17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ------NPNFTWRECDLNDFAALDKALQ 65
Cdd:cd05374     3 VLITGCSSGIGLALALALAAQGYRVIATARNPDKLEslgellNDNLEVLELDVTDEESIKAAVK 66

short chain dehydrogenase; This family contains a wide variety of dehydrogenases.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ---------NPNFTWRECDLNDFAALDKALQ 65
Cdd:pfam00106   3 ALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEavakelgalGGKALFIQGDVTDRAQVKALVE 69

Uncharacterized conserved protein YbjT, contains NAD(P)-binding and DUF2867 domains [General function prediction only];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSR---RAPDLQNPNFTWRECDLNDFAALDKALQ 65
Cdd:COG0702     2 ILVTGATGFIGRRVVRALLARGHPVRALVRdpeKAAALAAAGVEVVQGDLDDPESLAAALA 62

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1606831555   1 MPEPIQSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ---------NPNFTWRECDLNDFAALDKALQ 65
Cdd:COG0300     1 MSLTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEalaaelraaGARVEVVALDVTDPDAVAALAE 74

(S)-benzoin forming benzil reductase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1606831555   5 IQSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAP-------DLQNPNFTWRECDLNDFAALDKALQ 65
Cdd:PRK06924    1 MRYVIITGTSQGLGEAIANQLLEKGTHVISISRTENkeltklaEQYNSNLTFHSLDLQDVHELETNFN 68

short chain dehydrogenase; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQN-PNFTWRECDLNDFAALDKALQ 65
Cdd:PRK06179    7 ALVTGASSGIGRATAEKLARAGYRVFGTSRNPARAAPiPGVELLELDVTDDASVQAAVD 65

classical (c) SDRs; SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human prostaglandin dehydrogenase (PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, PGDH numbering) and/or an Asn (Asn-107, PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQN--------PNFTWRECDLNDFAALDKALQ 65
Cdd:cd05233     1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAElaaiealgGNAVAVQADVSDEEDVEALVE 66

short chain dehydrogenase; This family contains a wide variety of dehydrogenases.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ---------NPNFTWRECDLNDFAALDKALQ 65
Cdd:pfam00106   3 ALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEavakelgalGGKALFIQGDVTDRAQVKALVE 69

3-oxoacyl-ACP reductase FabG;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQN---------PNFTWRECDLNDFAALDKALQ 65
Cdd:PRK05653    6 KTALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEAlaaelraagGEARVLVFDVSDEAAVRALIE 74

retinol dehydrogenase (retinol-DH), Light dependent Protochlorophyllide (Pchlide) OxidoReductase (LPOR) and related proteins, classical (c) SDRs; Classical SDR subgroup containing retinol-DHs, LPORs, and related proteins. Retinol is processed by a medium chain alcohol dehydrogenase followed by retinol-DHs. Pchlide reductases act in chlorophyll biosynthesis. There are distinct enzymes that catalyze Pchlide reduction in light or dark conditions. Light-dependent reduction is via an NADP-dependent SDR, LPOR. Proteins in this subfamily share the glycine-rich NAD-binding motif of the classical SDRs, have a partial match to the canonical active site tetrad, but lack the typical active site Ser. This subgroup includes the human proteins: retinol dehydrogenase -12, -13 ,and -14, dehydrogenase/reductase SDR family member (DHRS)-12 , -13 and -X (a DHRS on chromosome X), and WWOX (WW domain-containing oxidoreductase), as well as a Neurospora crassa SDR encoded by the blue light inducible bli-4 gene. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ-----------NPNFTWRECDLNDFAALDKA 63
Cdd:cd05327     4 VVITGANSGIGKETARELAKRGAHVIIACRNEEKGEeaaaeikketgNAKVEVIQLDLSSLASVRQF 70

Extended (e) and atypical (a) SDRs; Extended or atypical short-chain dehydrogenases/reductases (SDRs, aka tyrosine-dependent oxidoreductases) are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSR---RAPDLQNPNFTWRECDLNDFAALDKALQ 65
Cdd:cd05226     1 ILILGATGFIGRALARELLEQGHEVTLLVRntkRLSKEDQEPVAVVEGDLRDLDSLSDAVQ 61

UDP-glucose 4 epimerase (G4E), subgroup 3, extended (e) SDRs; Members of this bacterial subgroup are identified as possible sugar epimerases, such as UDP-glucose 4 epimerase. However, while the NAD(P)-binding motif is fairly well conserved, not all members retain the canonical active site tetrad of the extended SDRs. UDP-glucose 4 epimerase (aka UDP-galactose-4-epimerase), is a homodimeric extended SDR. It catalyzes the NAD-dependent conversion of UDP-galactose to UDP-glucose, the final step in Leloir galactose synthesis. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEK--GLQVTGLSRRAPDLQNPNFTWRECDLNDFAALDK 62
Cdd:cd05240     1 ILVTGAAGGLGRLLARRLAASprVIGVDGLDRRRPPGSPPKVEYVRLDIRDPAAADV 57

NAD(P)H-binding;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1606831555  12 GASSGIGKAIVTRLLEKGLQVTGLSR---RAPDL-QNPNFTWRECDLNDFAALDKALQ 65
Cdd:pfam13460   1 GATGKIGRLLVKQLLARGHEVTALVRnpeKLADLeDHPGVEVVDGDVLDPDDLAEALA 58

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNPNFTWR----ECDLNDFAALDKALQ 65
Cdd:PRK07060   10 KSVLVTGASSGIGRACAVALAQRGARVVAAARNAAALDRLAGETGceplRLDVGDDAAIRAALA 73

triphenylmethane reductase (TMR)-like proteins, NMRa-like, atypical (a) SDRs; TMR is an atypical NADP-binding protein of the SDR family. It lacks the active site residues of the SDRs but has a glycine rich NAD(P)-binding motif that matches the extended SDRs. Proteins in this subgroup however, are more similar in length to the classical SDRs. TMR was identified as a reducer of triphenylmethane dyes, important environmental pollutants. This subgroup also includes Escherichia coli NADPH-dependent quinine oxidoreductase (QOR2), which catalyzes two-electron reduction of quinone; but is unlikely to play a major role in protecting against quinone cytotoxicity. Atypical SDRs are distinct from classical SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1606831555   9 LVTGASSGIGKAIVTRLLEKGLQVTGLSR---RAPDLQNPNFTWRECDLNDFAALDKALQ 65
Cdd:cd05269     2 LVTGATGKLGTAVVELLLAKVASVVALVRnpeKAKAFAADGVEVRQGDYDDPETLERAFE 61

sugar epimerase family protein;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNPNFTWRECDLNDFAALDKAL 64
Cdd:PRK05865    3 IAVTGASGVLGRGLTARLLSQGHEVVGIARHRPDSWPSSADFIAADIRDATAVESAM 59

atypical (a) SDRs, subgroup 5; This subgroup contains atypical SDRs, some of which are identified as putative NAD(P)-dependent epimerases, one as a putative NAD-dependent epimerase/dehydratase. Atypical SDRs are distinct from classical SDRs. Members of this subgroup have a glycine-rich NAD(P)-binding motif that is very similar to the extended SDRs, GXXGXXG, and binds NADP. Generally, this subgroup has poor conservation of the active site tetrad; however, individual sequences do contain matches to the YXXXK active site motif, the upstream Ser, and there is a highly conserved Asp in place of the usual active site Asn throughout the subgroup. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSR---RAPDLQNPNFTWRECDLNDFAALDKALQ 65
Cdd:cd05243     2 VLVVGATGKVGRHVVRELLDRGYQVRALVRdpsQAEKLEAAGAEVVVGDLTDAESLAAALE 62

SDR family oxidoreductase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNPNFTWRE---------CDLNDFAALDKALQ 65
Cdd:PRK07201  374 VLITGASSGIGRATAIKVAEAGATVFLVARNGEALDELVAEIRAkggtahaytCDLTDSAAVDHTVK 440

classical (c) SDR, subgroup 2; Short-chain dehydrogenases/reductases (SDRs, aka Tyrosine-dependent oxidoreductases) are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ-----NPNFTWRECDL---NDFAALDKAL 64
Cdd:cd05370     6 NTVLITGGTSGIGLALARKFLEAGNTVIITGRREERLAeakkeLPNIHTIVLDVgdaESVEALAEAL 72

xylulose reductase-like, classical (c) SDRs; Members of this subgroup include proteins identified as L-xylulose reductase (XR) and carbonyl reductase; they are members of the SDR family. XR, catalyzes the NADP-dependent reduction of L-xyulose and other sugars. Tetrameric mouse carbonyl reductase is involved in the metabolism of biogenic and xenobiotic carbonyl compounds. This subgroup also includes tetrameric chicken liver D-erythrulose reductase, which catalyzes the reduction of D-erythrulose to D-threitol. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNpnfTWREC--------DLNDFAALDKAL 64
Cdd:cd05351    10 ALVTGAGKGIGRATVKALAKAGARVVAVSRTQADLDS---LVRECpgiepvcvDLSDWDATEEAL 71

3-ketodihydrosphingosine reductase (KDSR) and related proteins, classical (c) SDR; These proteins include members identified as KDSR, ribitol type dehydrogenase, and others. The group shows strong conservation of the active site tetrad and glycine rich NAD-binding motif of the classical SDRs. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNP-------------NFTWRECDLNDFAALDKALQ 65
Cdd:cd08939     2 KHVLITGGSSGIGKALAKELVKEGANVIIVARSESKLEEAveeieaeanasgqKVSYISADLSDYEEVEQAFA 74

SDR family oxidoreductase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDL---------QNPNFTWRECDLNDFAALDKALQ 65
Cdd:PRK12826    7 RVALVTGAARGIGRAIAVRLAADGAEVIVVDICGDDAaataelveaAGGKARARQVDVRDRAALKAAVA 75

aldose dehydrogenase; Validated

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAP 40
Cdd:PRK06398    9 AIVTGGSQGIGKAVVNRLKEEGSNVINFDIKEP 41

SDR family oxidoreductase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQV-------TGLSRRAPDLQNPNFTWRECDLNDFAALDKAL 64
Cdd:PRK08267    2 KSIFITGAASGIGRATALLFAAEGWRVgaydineAGLAALAAELGAGNAWTGALDVTDRAAWDAAL 67

SDR family oxidoreductase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNPN---FTWRECDLNDFAALDKA 63
Cdd:PRK08017    3 KSVLITGCSSGIGLEAALELKRRGYRVLAACRKPDDVARMNslgFTGILLDLDDPESVERA 63

NmrA (a transcriptional regulator) and HSCARG (an NADPH sensor) like proteins, atypical (a) SDRs; NmrA and HSCARG like proteins. NmrA is a negative transcriptional regulator of various fungi, involved in the post-translational modulation of the GATA-type transcription factor AreA. NmrA lacks the canonical GXXGXXG NAD-binding motif and has altered residues at the catalytic triad, including a Met instead of the critical Tyr residue. NmrA may bind nucleotides but appears to lack any dehydrogenase activity. HSCARG has been identified as a putative NADP-sensing molecule, and redistributes and restructures in response to NADPH/NADP ratios. Like NmrA, it lacks most of the active site residues of the SDR family, but has an NAD(P)-binding motif similar to the extended SDR family, GXXGXXG. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Atypical SDRs are distinct from classical SDRs. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEK-GLQVTGLSR-----RAPDLQNPNFTWRECDLNDFAALDKALQ 65
Cdd:cd05251     1 ILVFGATGKQGGSVVRALLKDpGFKVRALTRdpsspAAKALAAPGVEVVQGDLDDPESLEAALK 64

UDP-glucose 4-epimerase (G4E), subgroup 5, extended (e) SDRs; This subgroup partially conserves the characteristic active site tetrad and NAD-binding motif of the extended SDRs, and has been identified as possible UDP-glucose 4-epimerase (aka UDP-galactose 4-epimerase), a homodimeric member of the extended SDR family. UDP-glucose 4-epimerase catalyzes the NAD-dependent conversion of UDP-galactose to UDP-glucose, the final step in Leloir galactose synthesis. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1606831555   7 SVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNPNF--TWRECDLNDFAALDKALQ 65
Cdd:cd05264     1 RVLIVGGNGFIGSHLVDALLEEGPQVRVFDRSIPPYELPLGgvDYIKGDYENRADLESALV 61

short chain dehydrogenase; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNPNFTWRECDL 54
Cdd:PRK06523   12 ALVTGGTKGIGAATVARLLEAGARVVTTARSRPDDLPEGVEFVAADL 58

dTDP-4-dehydrorhamnose reductase [Cell wall/membrane/envelope biogenesis];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRrapdlqnpnftwRECDLNDFAALDKALQ 65
Cdd:COG1091     2 ILVTGANGQLGRALVRLLAERGYEVVALDR------------SELDITDPEAVAALLE 47

classical (c) SDR, subgroup 6; These proteins are members of the classical SDR family, with a canonical active site tetrad and a fairly well conserved typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ---------NPNFTWRECDLNDFAALDKA 63
Cdd:cd05350     1 VLITGASSGIGRALAREFAKAGYNVALAARRTDRLDelkaellnpNPSVEVEILDVTDEERNQLV 65

bifunctional aldolase/short-chain dehydrogenase;

                          10        20
                  ....*....|....*....|....*...
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGL 35
Cdd:PRK08324  425 ALVTGAAGGIGKATAKRLAAEGACVVLA 452

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRR-----APDLQN----PNFTWRECDLND----FAALDKALQ 65
Cdd:cd05323     3 AIITGGASGIGLATAKLLLKKGAKVAILDRNenpgaAAELQAinpkVKATFVQCDVTSweqlAAAFKKAIE 73

gluconate 5-dehydrogenase (Ga5DH)-like, classical (c) SDRs; Ga5DH catalyzes the NADP-dependent conversion of carbon source D-gluconate and 5-keto-D-gluconate. This SDR subgroup has a classical Gly-rich NAD(P)-binding motif and a conserved active site tetrad pattern. However, it has been proposed that Arg104 (Streptococcus suis Ga5DH numbering), as well as an active site Ca2+, play a critical role in catalysis. In addition to Ga5DHs this subgroup contains Erwinia chrysanthemi KduD which is involved in pectin degradation, and is a putative 2,5-diketo-3-deoxygluconate dehydrogenase. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107,15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1606831555   9 LVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDL---------QNPNFTWRECDLNDFAALDKAL 64
Cdd:cd05347     9 LVTGASRGIGFGIASGLAEAGANIVINSRNEEKAeeaqqliekEGVEATAFTCDVSDEEAIKAAV 73

3-ketoacyl-(acyl-carrier-protein) reductase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQVT-GLSRRAPDLQNPNFTWR---------ECDLNDFAALDKALQ 65
Cdd:PRK12825    7 RVALVTGAARGLGRAIALRLARAGADVVvHYRSDEEAAEELVEAVEalgrraqavQADVTDKAALEAAVA 76

NAD dependent epimerase/dehydratase family enzyme [General function prediction only];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNPN--FTW 49
Cdd:COG1090     2 ILITGGTGFIGSALVAALLARGHEVVVLTRRPPKAPDEVtyVAW 45

3-oxoacyl-ACP reductase;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1606831555   4 PIQSVLVTGASSGIGKAIVTRLLEKGLQVTGLSR----RAPDLQN-PNFTW-----RECDLNDFAALDKAL 64
Cdd:PRK12824    1 MKKIALVTGAKRGIGSAIARELLNDGYRVIATYFsgndCAKDWFEeYGFTEdqvrlKELDVTDTEECAEAL 71

classical (c) SDR, subgroup 4; This subgroup has a canonical active site tetrad and a typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKGLQVTGLSR------RAPDLQNPNFTWRECDLNDFAALDKA 63
Cdd:cd08929     1 KAALVTGASRGIGEATARLLHAEGYRVGICARdearlaAAAAQELEGVLGLAGDVRDEADVRRA 64

rhamnulose-1-phosphate aldolase/alcohol dehydrogenase, classical (c) SDRs; This family has bifunctional proteins with an N-terminal aldolase and a C-terminal classical SDR domain. One member is identified as a rhamnulose-1-phosphate aldolase/alcohol dehydrogenase. The SDR domain has a canonical SDR glycine-rich NAD(P) binding motif and a match to the characteristic active site triad. However, it lacks an upstream active site Asn typical of SDRs. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1606831555   6 QSVLVTGASSGIGKAIVTRLLEKG-------LQVTGLSRRAPDLQNPNFTWR-ECDLNDFAALDKALQ 65
Cdd:cd08943     2 KVALVTGGASGIGLAIAKRLAAEGaavvvadIDPEIAEKVAEAAQGGPRALGvQCDVTSEAQVQSAFE 69

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1606831555   9 LVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ-----NPNFTW-RECDLNDFAALDKA 63
Cdd:PRK06180    8 LITGVSSGFGRALAQAALAAGHRVVGTVRSEAARAdfealHPDRALaRLLDVTDFDAIDAV 68

extended (e) SDRs; Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRR 38
Cdd:cd08946     1 ILVTGGAGFIGSHLVRRLLERGHEVVVIDRL 31

SDR family oxidoreductase;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1606831555   3 EPIQSVLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQ---------NPNFTWRECDLNDFAALDKALQ 65
Cdd:PRK07454    4 NSMPRALITGASSGIGKATALAFAKAGWDLALVARSQDALEalaaelrstGVKAAAYSIDLSNPEAIAPGIA 75

2,3 dihydro-2,3 dihydrozybenzoate dehydrogenases, classical (c) SDRs; 2,3 dihydro-2,3 dihydrozybenzoate dehydrogenase shares the characteristics of the classical SDRs. This subgroup includes Escherichai coli EntA which catalyzes the NAD+-dependent oxidation of 2,3-dihydro-2,3-dihydroxybenzoate to 2,3-dihydroxybenzoate during biosynthesis of the siderophore Enterobactin. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

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gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGLSRRAPDLQNPNFTWRE--CDLNDFAALDKALQ 65
Cdd:cd05331     1 VIVTGAAQGIGRAVARHLLQAGATVIALDLPFVLLLEYGDPLRLtpLDVADAAAVREVCS 60

UDP-N-acetylglucosamine 4-epimerase, extended (e) SDRs; This subgroup contains UDP-N-acetylglucosamine 4-epimerase of Pseudomonas aeruginosa, WbpP, an extended SDR, that catalyzes the NAD+ dependent conversion of UDP-GlcNAc and UDPGalNA to UDP-Glc and UDP-Gal. This subgroup has the characteristic active site tetrad and NAD-binding motif of the extended SDRs. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

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gi 1606831555   8 VLVTGASSGIGKAIVTRLLEKGLQVTGL----SRRAPDLQ--NPNFTWRECDLNDFAALDKALQ 65
Cdd:cd05256     2 VLVTGGAGFIGSHLVERLLERGHEVIVLdnlsTGKKENLPevKPNVKFIEGDIRDDELVEFAFE 65