carbonyl reductase sniffer-like, classical (c) SDRs; Sniffer is an NADPH-dependent carbonyl reductase of the classical SDR family. Studies in Drosophila melanogaster implicate Sniffer in the prevention of neurodegeneration due to aging and oxidative-stress. This subgroup also includes Rhodococcus sp. AD45 IsoH, which is an NAD-dependent 1-hydroxy-2-glutathionyl-2-methyl-3-butene dehydrogenase involved in isoprene metabolism, Aspergillus nidulans StcE encoded by a gene which is part of a proposed sterigmatocystin biosynthesis gene cluster, Bacillus circulans SANK 72073 BtrF encoded by a gene found in the butirosin biosynthesis gene cluster, and Aspergillus parasiticus nor-1 involved in the biosynthesis of aflatoxins. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   4 YLVTGATGGIGLEFCRQLCDRQ-ETVIAVCRHSSA--ELEQLGVRVES----GCDLTSP--EAVSKLASNLKGTTIDVLI 74
Cdd:cd05325     1 VLITGASRGIGLELVRQLLARGnNTVIATCRDPSAatELAALGASHSRlhilELDVTDEiaESAEAVAERLGDAGLDVLI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  75 NNAGIL-KRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQSG--SKIAIITSRMGSIGDNTSGSSYGYRMSKVAVSM 151
Cdd:cd05325    81 NNAGILhSYGPASEVDSEDLLEVFQVNVLGPLLLTQAFLPLLLKGarAKIINISSRVGSIGDNTSGGWYSYRASKAALNM 160

                         170       180
                  ....*....|....*....|....*....
gi 2783961385 152 AGKSLSHDLKPRGISVGILHPGLVRTRMT 180
Cdd:cd05325   161 LTKSLAVELKRDGITVVSLHPGWVRTDMG 189

carbonyl reductase sniffer-like, classical (c) SDRs; Sniffer is an NADPH-dependent carbonyl reductase of the classical SDR family. Studies in Drosophila melanogaster implicate Sniffer in the prevention of neurodegeneration due to aging and oxidative-stress. This subgroup also includes Rhodococcus sp. AD45 IsoH, which is an NAD-dependent 1-hydroxy-2-glutathionyl-2-methyl-3-butene dehydrogenase involved in isoprene metabolism, Aspergillus nidulans StcE encoded by a gene which is part of a proposed sterigmatocystin biosynthesis gene cluster, Bacillus circulans SANK 72073 BtrF encoded by a gene found in the butirosin biosynthesis gene cluster, and Aspergillus parasiticus nor-1 involved in the biosynthesis of aflatoxins. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   4 YLVTGATGGIGLEFCRQLCDRQ-ETVIAVCRHSSA--ELEQLGVRVES----GCDLTSP--EAVSKLASNLKGTTIDVLI 74
Cdd:cd05325     1 VLITGASRGIGLELVRQLLARGnNTVIATCRDPSAatELAALGASHSRlhilELDVTDEiaESAEAVAERLGDAGLDVLI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  75 NNAGIL-KRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQSG--SKIAIITSRMGSIGDNTSGSSYGYRMSKVAVSM 151
Cdd:cd05325    81 NNAGILhSYGPASEVDSEDLLEVFQVNVLGPLLLTQAFLPLLLKGarAKIINISSRVGSIGDNTSGGWYSYRASKAALNM 160

                         170       180
                  ....*....|....*....|....*....
gi 2783961385 152 AGKSLSHDLKPRGISVGILHPGLVRTRMT 180
Cdd:cd05325   161 LTKSLAVELKRDGITVVSLHPGWVRTDMG 189

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   5 LVTGATGGIGLEFCRQLCDRQETVIAVCRHSS------AELEQLGVRVES-GCDLTSPEAVSKLASNLKG--TTIDVLIN 75
Cdd:pfam00106   4 LVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEkleavaKELGALGGKALFiQGDVTDRAQVKALVEQAVErlGRLDILVN 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  76 NAGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHL--QSGSKIAIITS---RMGSIGdntsGSSYGyrMSKVAVS 150
Cdd:pfam00106  84 NAGITGLGPFSELSDEDWERVIDVNLTGVFNLTRAVLPAMikGSGGRIVNISSvagLVPYPG----GSAYS--ASKAAVI 157

                         170       180       190
                  ....*....|....*....|....*....|
gi 2783961385 151 MAGKSLSHDLKPRGISVGILHPGLVRTRMT 180
Cdd:pfam00106 158 GFTRSLALELAPHGIRVNAVAPGGVDTDMT 187

This enzymatic domain is part of bacterial polyketide synthases; It catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385    3 TYLVTGATGGIGLEFCRQLCDR-QETVIAVCR---------HSSAELEQLGVRVE-SGCDLTSPEAVSKLASNLKGT--T 69
Cdd:smart00822   2 TYLITGGLGGLGRALARWLAERgARRLVLLSRsgpdapgaaALLAELEAAGARVTvVACDVADRDALAAVLAAIPAVegP 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2783961385   70 IDVLINNAGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPH 114
Cdd:smart00822  82 LTGVIHAAGVLDDGVLASLTPERFAAVLAPKAAGAWNLHELTADL 126

carbonyl reductase sniffer-like, classical (c) SDRs; Sniffer is an NADPH-dependent carbonyl reductase of the classical SDR family. Studies in Drosophila melanogaster implicate Sniffer in the prevention of neurodegeneration due to aging and oxidative-stress. This subgroup also includes Rhodococcus sp. AD45 IsoH, which is an NAD-dependent 1-hydroxy-2-glutathionyl-2-methyl-3-butene dehydrogenase involved in isoprene metabolism, Aspergillus nidulans StcE encoded by a gene which is part of a proposed sterigmatocystin biosynthesis gene cluster, Bacillus circulans SANK 72073 BtrF encoded by a gene found in the butirosin biosynthesis gene cluster, and Aspergillus parasiticus nor-1 involved in the biosynthesis of aflatoxins. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   4 YLVTGATGGIGLEFCRQLCDRQ-ETVIAVCRHSSA--ELEQLGVRVES----GCDLTSP--EAVSKLASNLKGTTIDVLI 74
Cdd:cd05325     1 VLITGASRGIGLELVRQLLARGnNTVIATCRDPSAatELAALGASHSRlhilELDVTDEiaESAEAVAERLGDAGLDVLI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  75 NNAGIL-KRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQSG--SKIAIITSRMGSIGDNTSGSSYGYRMSKVAVSM 151
Cdd:cd05325    81 NNAGILhSYGPASEVDSEDLLEVFQVNVLGPLLLTQAFLPLLLKGarAKIINISSRVGSIGDNTSGGWYSYRASKAALNM 160

                         170       180
                  ....*....|....*....|....*....
gi 2783961385 152 AGKSLSHDLKPRGISVGILHPGLVRTRMT 180
Cdd:cd05325   161 LTKSLAVELKRDGITVVSLHPGWVRTDMG 189

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   3 TYLVTGATGGIGLEFCRQLCDRQETVIAVCRH-----SSAELEQLGVRVESgCDLTSPEAVSKLASNL--KGTTIDVLIN 75
Cdd:cd05374     2 VVLITGCSSGIGLALALALAAQGYRVIATARNpdkleSLGELLNDNLEVLE-LDVTDEESIKAAVKEVieRFGRIDVLVN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  76 NAGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHL--QSGSKIAIITSRMGSIGDNTSGSsygYRMSKVAVSMAG 153
Cdd:cd05374    81 NAGYGLFGPLEETSIEEVRELFEVNVFGPLRVTRAFLPLMrkQGSGRIVNVSSVAGLVPTPFLGP---YCASKAALEALS 157

                         170       180
                  ....*....|....*....|....*....
gi 2783961385 154 KSLSHDLKPRGISVGILHPGLVRTRMTNF 182
Cdd:cd05374   158 ESLRLELAPFGIKVTIIEPGPVRTGFADN 186

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   5 LVTGATGGIGLEFCRQLCDRQETVIAVCRHSSAELEQLGVRVESG------CDLTSPEAVSKLASNLKGT--TIDVLINN 76
Cdd:cd05233     2 LVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAAIEALGGnavavqADVSDEEDVEALVEEALEEfgRLDILVNN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  77 AGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHL--QSGSKIAIITSRMGSIGdntSGSSYGYRMSKVAVSMAGK 154
Cdd:cd05233    82 AGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMkkQGGGRIVNISSVAGLRP---LPGQAAYAASKAALEGLTR 158

                         170       180
                  ....*....|....*....|....*.
gi 2783961385 155 SLSHDLKPRGISVGILHPGLVRTRMT 180
Cdd:cd05233   159 SLALELAPYGIRVNAVAPGLVDTPML 184

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   5 LVTGATGGIGLEFCRQLCDRQETVIAVCRHSS------AELEQLGVRVES-GCDLTSPEAVSKLASNLKG--TTIDVLIN 75
Cdd:pfam00106   4 LVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEkleavaKELGALGGKALFiQGDVTDRAQVKALVEQAVErlGRLDILVN 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  76 NAGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHL--QSGSKIAIITS---RMGSIGdntsGSSYGyrMSKVAVS 150
Cdd:pfam00106  84 NAGITGLGPFSELSDEDWERVIDVNLTGVFNLTRAVLPAMikGSGGRIVNISSvagLVPYPG----GSAYS--ASKAAVI 157

                         170       180       190
                  ....*....|....*....|....*....|
gi 2783961385 151 MAGKSLSHDLKPRGISVGILHPGLVRTRMT 180
Cdd:pfam00106 158 GFTRSLALELAPHGIRVNAVAPGGVDTDMT 187

classical (c) SDR, subgroup 7; These proteins are members of the classical SDR family, with a canonical active site triad (and also an active site Asn) 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 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   3 TYLVTGATGGIGLEFCRQLCDRQET-VIAVCRH--SSAELEQL-GVRVES-GCDLTSPEAVSKLASNLKgtTIDVLINNA 77
Cdd:cd05354     5 TVLVTGANRGIGKAFVESLLAHGAKkVYAAVRDpgSAAHLVAKyGDKVVPlRLDVTDPESIKAAAAQAK--DVDVVINNA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  78 GILK-RNTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQSGSKIAIItsRMGSIGDNTSGSSYG-YRMSKVAVSMAGKS 155
Cdd:cd05354    83 GVLKpATLLEEGALEALKQEMDVNVFGLLRLAQAFAPVLKANGGGAIV--NLNSVASLKNFPAMGtYSASKSAAYSLTQG 160

                         170       180
                  ....*....|....*....|....*
gi 2783961385 156 LSHDLKPRGISVGILHPGLVRTRMT 180
Cdd:cd05354   161 LRAELAAQGTLVLSVHPGPIDTRMA 185

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   2 TTYLVTGATGGIGLEFCRQLCDR-QETVIAVCRHSSAeLEQLGVRVES-GCDLTSPEAVSKLASNLKGTTIdvLINNAGI 79
Cdd:PRK08264    7 KVVLVTGANRGIGRAFVEQLLARgAAKVYAAARDPES-VTDLGPRVVPlQLDVTDPASVAAAAEAASDVTI--LVNNAGI 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  80 LKRNT-LENLDFDSIRQQFEVNALGPLRVTQALLPHLQS--GSKIAIITSrMGSIGDNTSGSSYGyrMSKVAVSMAGKSL 156
Cdd:PRK08264   84 FRTGSlLLEGDEDALRAEMETNYFGPLAMARAFAPVLAAngGGAIVNVLS-VLSWVNFPNLGTYS--ASKAAAWSLTQAL 160

                         170       180
                  ....*....|....*....|....
gi 2783961385 157 SHDLKPRGISVGILHPGLVRTRMT 180
Cdd:PRK08264  161 RAELAPQGTRVLGVHPGPIDTDMA 184

HetN oxidoreductase-like, classical (c) SDR; This subgroup includes Anabaena sp. strain PCC 7120 HetN, a putative oxidoreductase involved in heterocyst differentiation, and related proteins. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   5 LVTGATGGIGLEFCRQLCDRQETVIAVCR--HSSAELEQLGVRVES-GCDLTSPEAVSKL--ASNLKGTTIDVLINNAGI 79
Cdd:cd08932     4 LVTGASRGIGIEIARALARDGYRVSLGLRnpEDLAALSASGGDVEAvPYDARDPEDARALvdALRDRFGRIDVLVHNAGI 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  80 LKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQ-SGS-KIAIITSRMGSIgdnTSGSSYGYRMSKVAVSMAGKSLS 157
Cdd:cd08932    84 GRPTTLREGSDAELEAHFSINVIAPAELTRALLPALReAGSgRVVFLNSLSGKR---VLAGNAGYSASKFALRALAHALR 160

                         170       180
                  ....*....|....*....|...
gi 2783961385 158 HDLKPRGISVGILHPGLVRTRMT 180
Cdd:cd08932   161 QEGWDHGVRVSAVCPGFVDTPMA 183

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   5 LVTGATGGIGLEFCRQLCDRQETVIAVCRHS-------SAELEQLGVRVE-SGCDLTSPEAVSKLASNLKGT--TIDVLI 74
Cdd:PRK12825   10 LVTGAARGLGRAIALRLARAGADVVVHYRSDeeaaeelVEAVEALGRRAQaVQADVTDKAALEAAVAAAVERfgRIDILV 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  75 NNAGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHL--QSGSKIAIITSRMGSIGdnTSGSSyGYRMSKVAVSMA 152
Cdd:PRK12825   90 NNAGIFEDKPLADMSDDEWDEVIDVNLSGVFHLLRAVVPPMrkQRGGRIVNISSVAGLPG--WPGRS-NYAAAKAGLVGL 166

                         170       180
                  ....*....|....*....|....*....
gi 2783961385 153 GKSLSHDLKPRGISVGILHPGLVRTRMTN 181
Cdd:PRK12825  167 TKALARELAEYGITVNMVAPGDIDTDMKE 195

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   1 MTTYLVTGATGGIGLEFCRQLCDRQETVIAVCR--HSSAELEQL-GVRVESgCDLTSPEAVSKLASNLKGTTIDVLINNA 77
Cdd:PRK08177    1 KRTALIIGASRGLGLGLVDRLLERGWQVTATVRgpQQDTALQALpGVHIEK-LDMNDPASLDQLLQRLQGQRFDLLFVNA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  78 GIL--KRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQSGSK-IAIITSRMGSIGDNTSGSSYGYRMSKVAVSMAGK 154
Cdd:PRK08177   80 GISgpAHQSAADATAAEIGQLFLTNAIAPIRLARRLLGQVRPGQGvLAFMSSQLGSVELPDGGEMPLYKASKAALNSMTR 159

                         170       180
                  ....*....|....*....|....*
gi 2783961385 155 SLSHDLKPRGISVGILHPGLVRTRM 179
Cdd:PRK08177  160 SFVAELGEPTLTVLSMHPGWVKTDM 184

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   5 LVTGATGGIGLEFCRQLCDRQETVIAVCRHSS-------AELEQLGVRV-ESGCDLTSPEAVSKLASNLKGT--TIDVLI 74
Cdd:PRK05557    9 LVTGASRGIGRAIAERLAAQGANVVINYASSEagaealvAEIGALGGKAlAVQGDVSDAESVERAVDEAKAEfgGVDILV 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  75 NNAGILKRNTLENL---DFDSIrqqFEVNALGPLRVTQALLPHL--QSGSKIAIITS---RMGSIGdntsGSSYGyrMSK 146
Cdd:PRK05557   89 NNAGITRDNLLMRMkeeDWDRV---IDTNLTGVFNLTKAVARPMmkQRSGRIINISSvvgLMGNPG----QANYA--ASK 159

                         170       180       190
                  ....*....|....*....|....*....|....
gi 2783961385 147 VAVSMAGKSLSHDLKPRGISVGILHPGLVRTRMT 180
Cdd:PRK05557  160 AGVIGFTKSLARELASRGITVNAVAPGFIETDMT 193

17-beta-hydroxysteroid dehydrogenases (17beta-HSDs) types -1, -3, and -12, -like, classical (c) SDRs; This subgroup includes various 17-beta-hydroxysteroid dehydrogenases and 3-ketoacyl-CoA reductase, these are members of the SDR family, and contain the canonical active site tetrad and glycine-rich NAD-binding motif of the classical SDRs. 3-ketoacyl-CoA reductase (KAR, aka 17beta-HSD type 12, encoded by HSD17B12) acts in fatty acid elongation; 17beta- hydroxysteroid dehydrogenases are isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. 17beta-estradiol dehydrogenase (aka 17beta-HSD type 1, encoded by HSD17B1) converts estrone to estradiol. Estradiol is the predominant female sex hormone. 17beta-HSD type 3 (aka testosterone 17-beta-dehydrogenase 3, encoded by HSD17B3) catalyses the reduction of androstenedione to testosterone, it also accepts estrogens as substrates. This subgroup also contains a putative steroid dehydrogenase let-767 from Caenorhabditis elegans, mutation in which results in hypersensitivity to cholesterol limitation. 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   6 VTGATGGIGLEFCRQLCDRQETVIAVCRHSS------AELE-QLGVRVES-GCDLT-SPEAVSKLASNLKGTTIDVLINN 76
Cdd:cd05356     6 VTGATDGIGKAYAEELAKRGFNVILISRTQEkldavaKEIEeKYGVETKTiAADFSaGDDIYERIEKELEGLDIGILVNN 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  77 AGILKR--NTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQSGSKIAIITsrMGSI-GDNTS--GSSYGyrMSKVAVSM 151
Cdd:cd05356    86 VGISHSipEYFLETPEDELQDIINVNVMATLKMTRLILPGMVKRKKGAIVN--ISSFaGLIPTplLATYS--ASKAFLDF 161

                         170       180       190
                  ....*....|....*....|....*....|..
gi 2783961385 152 AGKSLSHDLKPRGISVGILHPGLVRTRMTNFT 183
Cdd:cd05356   162 FSRALYEEYKSQGIDVQSLLPYLVATKMSKIR 193

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   5 LVTGATGGIGLEFCRQLCDRQETVIAVCRHSSAeLEQL------GVRVES-GCDLTSPEAVSKL-ASNLKGTTIDVLINN 76
Cdd:PRK09072    9 LLTGASGGIGQALAEALAAAGARLLLVGRNAEK-LEALaarlpyPGRHRWvVADLTSEAGREAVlARAREMGGINVLINN 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  77 AGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHL--QSGSKIAIITSRMGSIGdnTSGSSyGYRMSKVAVSMAGK 154
Cdd:PRK09072   88 AGVNHFALLEDQDPEAIERLLALNLTAPMQLTRALLPLLraQPSAMVVNVGSTFGSIG--YPGYA-SYCASKFALRGFSE 164

                         170       180
                  ....*....|....*....|....*
gi 2783961385 155 SLSHDLKPRGISVGILHPGLVRTRM 179
Cdd:PRK09072  165 ALRRELADTGVRVLYLAPRATRTAM 189

tetrahydroxynaphthalene/trihydroxynaphthalene reductase-like, classical (c) SDRs; 1,3,6,8-tetrahydroxynaphthalene reductase (4HNR) of Magnaporthe grisea and the related 1,3,8-trihydroxynaphthalene reductase (3HNR) are typical members of the SDR family containing the canonical glycine rich NAD(P)-binding site and active site tetrad, and function in fungal melanin biosynthesis. This subgroup also includes an SDR from Norway spruce that may function to protect against both biotic and abitoic stress. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   5 LVTGATGGIGLEFCRQLCDRQETViAVCRHSS--------AELEQLGVRVES-GCDLTSPEAVSKL--ASNLKGTTIDVL 73
Cdd:cd05362     7 LVTGASRGIGRAIAKRLARDGASV-VVNYASSkaaaeevvAEIEAAGGKAIAvQADVSDPSQVARLfdAAEKAFGGVDIL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  74 INNAGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQSGSKIAIITSrmgSIGDNTSGSSYGYRMSKVAVSMAG 153
Cdd:cd05362    86 VNNAGVMLKKPIAETSEEEFDRMFTVNTKGAFFVLQEAAKRLRDGGRIINISS---SLTAAYTPNYGAYAGSKAAVEAFT 162

                         170       180
                  ....*....|....*....|....*.
gi 2783961385 154 KSLSHDLKPRGISVGILHPGLVRTRM 179
Cdd:cd05362   163 RVLAKELGGRGITVNAVAPGPVDTDM 188

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385   1 MTTYLVTGATGGIGLEFCRQLCDRQETVIAVCRHSSA--ELEQLG-----VRVesgCDLTSPEAVSKLASNLKGT--TID 71
Cdd:PRK06180    4 MKTWLITGVSSGFGRALAQAALAAGHRVVGTVRSEAAraDFEALHpdralARL---LDVTDFDAIDAVVADAEATfgPID 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2783961385  72 VLINNAGILKRNTLENLDFDSIRQQFEVNALGPLRVTQALLPHLQ---SGSKIAiITSrMGSIGDNtSGSSYgYRMSKVA 148
Cdd:PRK06180   81 VLVNNAGYGHEGAIEESPLAEMRRQFEVNVFGAVAMTKAVLPGMRarrRGHIVN-ITS-MGGLITM-PGIGY-YCGSKFA 156

                         170       180
                  ....*....|....*....|....*....
gi 2783961385 149 VSMAGKSLSHDLKPRGISVGILHPGLVRT 177
Cdd:PRK06180  157 LEGISESLAKEVAPFGIHVTAVEPGSFRT 185