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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   2 KIFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTLVKKENVSYVSFDLTWSvEKMTEAFKGIDVLIFAAGS---QGK 78
Cdd:cd05243     1 KVLVVGATGKVGRHVVRELLDRGYQVRALVRDPSQAEKLEAAGAEVVVGDLTDA-ESLAAALEGIDAVISAAGSggkGGP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092  79 NLLQVDLDGAIKTVIAAENAHVSRYLMVSAVYADEPAKWPESMTDYYITKHYADEWLKRTNLDFVILQPVTLTNDEEVT- 157
Cdd:cd05243    80 RTEAVDYDGNINLIDAAKKAGVKRFVLVSSIGADKPSHPLEALGPYLDAKRKAEDYLRASGLDYTIVRPGGLTDDPAGTg 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1534073092 158 SIQLTKPNEKASKTITRSTVAAVLAALVEETDISRTTLVLSEG 200
Cdd:cd05243   160 RVVLGGDGTRLDGPISRADVAEVLAEALDTPAAIGKTFELGGG 202

Tic62-NAD(P)-related group II protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   2 KIFVVGANGQIGRHLIKDLAPSSHEIFAGVRDV--ASQTLVKKENVSYVSFDLTWSVEKMTEAF-KGIDVLIFAAGSQ-G 77
Cdd:PLN00141   19 TVFVAGATGRTGKRIVEQLLAKGFAVKAGVRDVdkAKTSLPQDPSLQIVRADVTEGSDKLVEAIgDDSDAVICATGFRrS 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092  78 KNLL---QVDLDGAIKTVIAAENAHVSRYLMVSAVYADEpAKWPESMTDYYI----------TKHYADEWLKRTNLDFVI 144
Cdd:PLN00141   99 FDPFapwKVDNFGTVNLVEACRKAGVTRFILVSSILVNG-AAMGQILNPAYIflnlfgltlvAKLQAEKYIRKSGINYTI 177

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1534073092 145 LQPVTLTNDEEVTSIQLTKPNEKASKTITRSTVA--AVLAALVEET 188
Cdd:PLN00141  178 VRPGGLTNDPPTGNIVMEPEDTLYEGSISRDQVAevAVEALLCPES 223

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   2 KIFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTLVKKENVSYVSFDLTWSvEKMTEAFKGIDVLIFAAGS---QGK 78
Cdd:cd05243     1 KVLVVGATGKVGRHVVRELLDRGYQVRALVRDPSQAEKLEAAGAEVVVGDLTDA-ESLAAALEGIDAVISAAGSggkGGP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092  79 NLLQVDLDGAIKTVIAAENAHVSRYLMVSAVYADEPAKWPESMTDYYITKHYADEWLKRTNLDFVILQPVTLTNDEEVT- 157
Cdd:cd05243    80 RTEAVDYDGNINLIDAAKKAGVKRFVLVSSIGADKPSHPLEALGPYLDAKRKAEDYLRASGLDYTIVRPGGLTDDPAGTg 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1534073092 158 SIQLTKPNEKASKTITRSTVAAVLAALVEETDISRTTLVLSEG 200
Cdd:cd05243   160 RVVLGGDGTRLDGPISRADVAEVLAEALDTPAAIGKTFELGGG 202

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   2 KIFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTLVKKENVSYVSFDLTwSVEKMTEAFKGIDVLIFAAGSQGKNLL 81
Cdd:COG0702     1 KILVTGATGFIGRRVVRALLARGHPVRALVRDPEKAAALAAAGVEVVQGDLD-DPESLAAALAGVDAVFLLVPSGPGGDF 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1534073092  82 QVDLDGAIKTVIAAENAHVSRYLMVSAVYADEPAKWPesmtdYYITKHYADEWLKRTNLDFVILQP 147
Cdd:COG0702    80 AVDVEGARNLADAAKAAGVKRIVYLSALGADRDSPSP-----YLRAKAAVEEALRASGLPYTILRP 140

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   3 IFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTLVKKENVSYVSFDLTwSVEKMTEAFKGIDVLIFAAGSQGKNLLQ 82
Cdd:cd05269     1 ILVTGATGKLGTAVVELLLAKVASVVALVRNPEKAKAFAADGVEVRQGDYD-DPETLERAFEGVDRLLLISPSDLEDRIQ 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1534073092  83 VDldgaiKTVI-AAENAHVSRYLMVSAVYADEPAkwPESMTDYYItkhYADEWLKRTNLDFVILQP 147
Cdd:cd05269    80 QH-----KNFIdAAKQAGVKHIVYLSASGADEDS--PFLLARDHG---ATEKYLEASGIPYTILRP 135

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   3 IFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTLVKKENVSYVSFDLTWSvEKMTEAFKGIDVLIFAAGS--QGKNL 80
Cdd:cd05226     1 ILILGATGFIGRALARELLEQGHEVTLLVRNTKRLSKEDQEPVAVVEGDLRDL-DSLSDAVQGVDVVIHLAGAprDTRDF 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1534073092  81 LQVDLDGAIKTVIAAENAHVSRYLMVSA--VYADEPAKWPESMTDYYITKHYADEWLKR-TNLDFVILQPVTLTND 153
Cdd:cd05226    80 CEVDVEGTRNVLEAAKEAGVKHFIFISSlgAYGDLHEETEPSPSSPYLAVKAKTEAVLReASLPYTIVRPGVIYGD 155

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, subunit 9, 39 kDa, (NDUFA9) -like, atypical (a) SDRs; This subgroup of extended SDR-like proteins are atypical SDRs. They have a glycine-rich NAD(P)-binding motif similar to the typical SDRs, GXXGXXG, and have the YXXXK active site motif (though not the other residues of the SDR tetrad). Members identified include NDUFA9 (mitochondrial) and putative nucleoside-diphosphate-sugar epimerase. 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   1 MKIFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTLVKKEN----VSYVSFDLTWSvEKMTEAFKGIDVLIFAAGS- 75
Cdd:cd05271     1 MVVTVFGATGFIGRYVVNRLAKRGSQVIVPYRCEAYARRLLVMGdlgqVLFVEFDLRDD-ESIRKALEGSDVVINLVGRl 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1534073092  76 -QGKN--LLQVDLDGAIKTVIAAENAHVSRYLMVSAVYADepakwPESMTDYYITKHYADEWLKRTNLDFVILQP 147
Cdd:cd05271    80 yETKNfsFEDVHVEGPERLAKAAKEAGVERLIHISALGAD-----ANSPSKYLRSKAEGEEAVREAFPEATIVRP 149

biliverdin IX beta reductase (BVR-B, aka flavin reductase)-like proteins; atypical (a) SDRs; Human BVR-B catalyzes pyridine nucleotide-dependent production of bilirubin-IX beta during fetal development; in the adult BVR-B has flavin and ferric reductase activities. Human BVR-B catalyzes the reduction of FMN, FAD, and riboflavin. Recognition of flavin occurs mostly by hydrophobic interactions, accounting for the broad substrate specificity. Atypical SDRs are distinct from classical SDRs. BVR-B does not share the key catalytic triad, or conserved tyrosine typical of SDRs. The glycine-rich NADP-binding motif of BVR-B is GXXGXXG, which is similar but not identical to the pattern seen in extended SDRs. 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   2 KIFVVGANGQIGRHLIKDLAPSSHEIFAGVRDvASQTLVKKENVSYVSFDLTwSVEKMTEAFKGIDVLIFAAGSqGKNLL 81
Cdd:cd05244     1 KIAIIGATGRTGSAIVREALARGHEVTALVRD-PAKLPAEHEKLKVVQGDVL-DLEDVKEALEGQDAVISALGT-RNDLS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092  82 QVDL--DGAIKTVIAAENAHVSRYLMVSAVYADE--------------PAKWPESMTDyyitKHYADEWLKRTNLDFVIL 145
Cdd:cd05244    78 PTTLhsEGTRNIVSAMKAAGVKRLIVVGGAGSLDdrpkvtlvldtllfPPALRRVAED----HARMLKVLRESGLDWTAV 153

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1534073092 146 QPVTLTNDEEVTSIQLTKP--NEKASKTITRSTVA-AVLAALVEET 188
Cdd:cd05244   154 RPPALFDGGATGGYYRVELlvDAKGGSRISRADLAiFMLDELETPE 199

NmrA-like family; NmrA is a negative transcriptional regulator involved in the post-translational modification of the transcription factor AreA. NmrA is part of a system controlling nitrogen metabolite repression in fungi. This family only contains a few sequences as iteration results in significant matches to other Rossmann fold families.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   3 IFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTL--VKKENVSYVSFDLTwSVEKMTEAFKGIDVLIFAAGSQGKNL 80
Cdd:pfam05368   1 ILVFGATGQQGGSVVRASLKAGHKVRALVRDPKSELAksLKEAGVELVKGDLD-DKESLVEALKGVDVVFSVTGFWAGKE 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1534073092  81 LQvdlDGAiKTVIAAENAHVSRYL------MVSAVYADEPAK 116
Cdd:pfam05368  80 IE---DGK-KLADAAKEAGVKHFIpssfgnDNDISNGVEPAV 117

atypical (a) SDRs, subgroup 2; This subgroup contains atypical SDRs, one member is identified as Escherichia coli protein ybjT, function unknown. Atypical SDRs are distinct from classical SDRs. Members of this subgroup have a glycine-rich NAD(P)-binding motif consensus that generally matches the extended SDRs, TGXXGXXG, but lacks the characteristic active site residues of the SDRs. This subgroup has basic residues (HXXXR) in place of the active site motif YXXXK, these may have a catalytic role. 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   3 IFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQT-LVKKENVSYVSFDLTWSvEKMTEAFKGIDVLIFAAGS--QGKN 79
Cdd:cd05245     1 VLVTGATGYVGGRLVPRLLQEGHQVRALVRSPEKLAdRPWSERVTVVRGDLEDP-ESLRAALEGIDTAYYLVHSmgSGGD 79

                          90       100
                  ....*....|....*....|....*..
gi 1534073092  80 LLQVDLDGAIKTVIAAENAHVSR--YL 104
Cdd:cd05245    80 FEEADRRAARNFARAARAAGVKRiiYL 106

UDP-glucose 4 epimerase, subgroup 4, extended (e) 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. This subgroup is comprised of bacterial proteins, and includes the Staphylococcus aureus capsular polysaccharide Cap5N, which may have a role in the synthesis of UDP-N-acetyl-d-fucosamine. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   2 KIFVVGANGQIGRHLIKDLAPSSHEIFAGVRdvasqTLVKKENvSYVSFDLtWSVEKMTEAFKGIDVLIFAAG------- 74
Cdd:cd05232     1 KVLVTGANGFIGRALVDKLLSRGEEVRIAVR-----NAENAEP-SVVLAEL-PDIDSFTDLFLGVDAVVHLAArvhvmnd 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092  75 SQGKNLL---QVDLDGAIKTVIAAENAHVSRYLMVSAVYA------DEP--AKWPESMTDYY-ITKHYADEWLK----RT 138
Cdd:cd05232    74 QGADPLSdyrKVNTELTRRLARAAARQGVKRFVFLSSVKVngegtvGAPfdETDPPAPQDAYgRSKLEAERALLelgaSD 153

                  ....*....
gi 1534073092 139 NLDFVILQP 147
Cdd:cd05232   154 GMEVVILRP 162

Ycf39; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   1 MKIFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTLVKKENVSYVSFDLTWSvEKMTEAFKGIDVLIFAAGSQGK-- 78
Cdd:CHL00194    1 MSLLVIGATGTLGRQIVRQALDEGYQVRCLVRNLRKASFLKEWGAELVYGDLSLP-ETLPPSFKGVTAIIDASTSRPSdl 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1534073092  79 -NLLQVDLDGAIKTVIAAENAHVSRYLMVSAVYADepaKWPesmtdyYIT----KHYADEWLKRTNLDFVILQP 147
Cdd:CHL00194   80 yNAKQIDWDGKLALIEAAKAAKIKRFIFFSILNAE---QYP------YIPlmklKSDIEQKLKKSGIPYTIFRL 144

Pseudomonas fluorescens MupV-like, extended (e) SDRs; This subgroup of extended SDR family domains have the characteristic active site tetrad and a well-conserved NAD(P)-binding motif. This subgroup is not well characterized, its members are annotated as having a variety of putative functions. One characterized member is Pseudomonas fluorescens MupV a protein involved in the biosynthesis of Mupirocin, a polyketide-derived antibiotic. 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   3 IFVVGANGQIGRHLIKDLAPSSHEIFAGVRDVASQTLVKKEN--------VSYVSFDLT-----WSVEKMTEAFKGIDVL 69
Cdd:cd05263     1 VFVTGGTGFLGRHLVKRLLENGFKVLVLVRSESLGEAHERIEeagleadrVRVLEGDLTqpnlgLSAAASRELAGKVDHV 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1534073092  70 IFAAGS---QGKN--LLQVDLDGAiKTVIA-AENAHVSRYLMVSAVYAD 112
Cdd:cd05263    81 IHCAASydfQAPNedAWRTNIDGT-EHVLElAARLDIQRFHYVSTAYVA 128

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 1534073092   3 IFVVGANGQIGRHLIKDLAPSSHE-IFAGVRDVASQT-----LVKKENVSYVSFDLTW----SVEKMTEAFK--GIDVLI 70
Cdd:cd05325     1 VLITGASRGIGLELVRQLLARGNNtVIATCRDPSAATelaalGASHSRLHILELDVTDeiaeSAEAVAERLGdaGLDVLI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092  71 FAAG--SQGKNLLQVDLDGAIKT----VIAA-----------ENAHVSRYLMVSAVYADEPAKWPESMTDY--------Y 125
Cdd:cd05325    81 NNAGilHSYGPASEVDSEDLLEVfqvnVLGPllltqaflpllLKGARAKIINISSRVGSIGDNTSGGWYSYraskaalnM 160

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1534073092 126 ITKHYADEwLKRTNLDFVILQPVTLTNDeevtsiqLTKPNEKASKTITRSTVAAVLAALVEETDISRT 193
Cdd:cd05325   161 LTKSLAVE-LKRDGITVVSLHPGWVRTD-------MGGPFAKNKGPITPEESVAGLLKVIDNLNEEDS 220

N-terminal NAD(P)-binding domain of Vibrio cholerae aspartate beta-semialdehyde dehydrogenase 2 (ASADH2) and similar proteins; The family corresponds to a new branch of bacterial ASADH enzymes that has a similar overall fold and domain organization but sharing less sequence homology with the other bacterial ASADHs. The second isoform of ASADH in Vibrio cholerae is one of the prototypes of this family. It also includes ASADHs from Streptococcus pneumoniae, Mycobacterium tuberculosis, Thermus thermophilus, as well as from eukaryotes. ASADH (EC 1.2.1.11), also called ASA dehydrogenase (ASD), or aspartate-beta-semialdehyde dehydrogenase, catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate, which is the second step of the aspartate biosynthetic pathway. ASA can either be further reduced to homoserine, which leads to methionine, threonine, or isoleucine, or it can be condensed with pyruvate and cyclized into dihydrodipicolinate, and then converted into diaminopimelate, a component of bacterial cell walls, and finally decarboxylated to produce lysine. ASADH contains an N-terminal Rossmann fold NAD(P) binding domain and a C-terminal glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-like catalytic domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1534073092   1 MKIFVVGANGQIGRHLIKDLAPSSHEIfAGVRDVASQTLVKKEnvsyVSF-DLTWSVEKMTE-AFKGIDVLIFAAGS 75
Cdd:cd02316     1 YNVAIVGATGAVGQEMLKVLEERNFPV-SELRLLASARSAGKT----LEFkGKELTVEELTEdSFKGVDIALFSAGG 72

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 1534073092   3 IFVVGANGQIGRHLIKD-LAPSSHEIFAGVRDVASQT-LVKK--ENVSYVSFDLT--WSVEKMTEAFKGIDVLIFAAG-S 75
Cdd:cd05354     6 VLVTGANRGIGKAFVESlLAHGAKKVYAAVRDPGSAAhLVAKygDKVVPLRLDVTdpESIKAAAAQAKDVDVVINNAGvL 85

                          90
                  ....*....|....*
gi 1534073092  76 QGKNLLQVDLDGAIK 90
Cdd:cd05354    86 KPATLLEEGALEALK 100

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   3 IFVVGANGQIGRHLIKDLAPSSHEIFAGVRD------VASQTLVKKENVSYVSFDLTWS------VEKMTEAFKGIDVLI 70
Cdd:COG0300     8 VLITGASSGIGRALARALAARGARVVLVARDaerleaLAAELRAAGARVEVVALDVTDPdavaalAEAVLARFGPIDVLV 87

                          90       100
                  ....*....|....*....|....*
gi 1534073092  71 FAAG-SQGKNLLQVDLDgAIKTVIA 94
Cdd:COG0300    88 NNAGvGGGGPFEELDLE-DLRRVFE 111

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   1 MKIFVVGANGQIGRHLIKDLAPSSHE--IFAGVRdvASQTLVKKENVSYVSFDLT--WSVEKMTEAFKGIDVLIFAAG-- 74
Cdd:PRK09009    1 MNILIVGGSGGIGKAMVKQLLERYPDatVHATYR--HHKPDFQHDNVQWHALDVTdeAEIKQLSEQFTQLDWLINCVGml 78

                          90
                  ....*....|....*..
gi 1534073092  75 ---SQG--KNLLQVDLD 86
Cdd:PRK09009   79 htqDKGpeKSLQALDAD 95

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092   2 KIFVVGANGQIGRHLIKDLAPSSHEIfAGVRDVAS--QTLVK--KENVSYVSFDLTwSVEKMTEAFKGIDVlIFAAGSQG 77
Cdd:cd05256     1 RVLVTGGAGFIGSHLVERLLERGHEV-IVLDNLSTgkKENLPevKPNVKFIEGDIR-DDELVEFAFEGVDY-VFHQAAQA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1534073092  78 KNL---------LQVDLDGAIKTVIAAENAHVSR--YLMVSAVYADEPAK--------WPESmtDYYITK----HYADEW 134
Cdd:cd05256    78 SVPrsiedpikdHEVNVLGTLNLLEAARKAGVKRfvYASSSSVYGDPPYLpkdedhppNPLS--PYAVSKyageLYCQVF 155

                         170
                  ....*....|.
gi 1534073092 135 LKRTNLDFVIL 145
Cdd:cd05256   156 ARLYGLPTVSL 166

aspartate-semialdehyde dehydrogenase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1534073092   1 MKIFVVGANGQIGRHLIKDLAPSSHEIfAGVRDVASQTLVKKEnvsyVSF-DLTWSVEKMTEA-FKGIDVLIFAAGS 75
Cdd:PRK14874    2 YNVAVVGATGAVGREMLNILEERNFPV-DKLRLLASARSAGKE----LSFkGKELKVEDLTTFdFSGVDIALFSAGG 73

atypical (a) SDRs, subgroup 8; This subgroup contains atypical SDRs of unknown function. Proteins in this subgroup have a glycine-rich NAD(P)-binding motif consensus that resembles that of the extended SDRs, (GXXGXXG or GGXGXXG), but lacks the characteristic active site residues of the SDRs. A Cys often replaces the usual Lys of the YXXXK active site motif, while the upstream Ser is generally present and Arg replaces the usual Asn. 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1534073092   2 KIFVVGANGQIGRHLIKDLAPSSHEIFAGVRDvASQTLVKKENVsyvsfdlTW-SVEKMTEAFKGIDVLIFAAG 74
Cdd:cd05242     1 KIVITGGTGFIGRALTRRLTAAGHEVVVLSRR-PGKAEGLAEVI-------TWdGLSLGPWELPGADAVINLAG 66