Rossmann-fold NAD(P)(+)-binding proteins; A large family of proteins that share a Rossmann-fold NAD(P)H/NAD(P)(+) binding (NADB) domain. The NADB domain is found in numerous dehydrogenases of metabolic pathways such as glycolysis, and many other redox enzymes. NAD binding involves numerous hydrogen-bonds and van der Waals contacts, in particular H-bonding of residues in a turn between the first strand and the subsequent helix of the Rossmann-fold topology. Characteristically, this turn exhibits a consensus binding pattern similar to GXGXXG, in which the first 2 glycines participate in NAD(P)-binding, and the third facilitates close packing of the helix to the beta-strand. Typically, proteins in this family contain a second domain in addition to the NADB domain, which is responsible for specifically binding a substrate and catalyzing a particular enzymatic reaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504427501   5 VLLAGGTGYIGKSLIKEL-----------RDTTTLHTISQypksqsHADTTVIKGDIYHYADVLRAMEGMDIAVYFLdpt 73
Cdd:cd05245    1 VLVTGATGYVGGRLVPRLlqeghqvralvRSPEKLADRPW------SERVTVVRGDLEDPESLRAALEGIDTAYYLV--- 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 504427501  74 kHSAKLTRALAkDLNLIAADNFGRAAAKQQVKEIIYVRGSQFDE-----------ETVKQLGAYGVPI 130
Cdd:cd05245   72 -HSMGSGGDFE-EADRRAARNFARAARAAGVKRIIYLGGLIPKGeelsphlrsraEVGEILRAGGVPV 137

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 504427501   5 VLLAGGTGYIGKSLIKEL-----------RDTTTLHTISQypksqsHADTTVIKGDIYHYADVLRAMEGMDIAVYFLdpt 73
Cdd:cd05245    1 VLVTGATGYVGGRLVPRLlqeghqvralvRSPEKLADRPW------SERVTVVRGDLEDPESLRAALEGIDTAYYLV--- 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 504427501  74 kHSAKLTRALAkDLNLIAADNFGRAAAKQQVKEIIYVRGSQFDE-----------ETVKQLGAYGVPI 130
Cdd:cd05245   72 -HSMGSGGDFE-EADRRAARNFARAARAAGVKRIIYLGGLIPKGeelsphlrsraEVGEILRAGGVPV 137

NAD(P)H-binding;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504427501    9 GGTGYIGKSLIKELRD---TTTLHT--ISQYPKSQSHADTTVIKGDIYHYADVLRAMEGMDiAVYF-LDPTKHSAKLTRA 82
Cdd:pfam13460   1 GATGKIGRLLVKQLLArghEVTALVrnPEKLADLEDHPGVEVVDGDVLDPDDLAEALAGQD-AVISaLGGGGTDETGAKN 79

                          90       100
                  ....*....|....*....|....*...
gi 504427501   83 LAKdlnliaadnfgrAAAKQQVKEIIYV 110
Cdd:pfam13460  80 IID------------AAKAAGVKRFVLV 95

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 504427501   5 VLLAGGTGYIGKSLIKEL-----------RDTTTLHTISQypksqsHADTTVIKGDIYHYADVLRAMEGMDIAVYFLdpt 73
Cdd:cd05245    1 VLVTGATGYVGGRLVPRLlqeghqvralvRSPEKLADRPW------SERVTVVRGDLEDPESLRAALEGIDTAYYLV--- 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 504427501  74 kHSAKLTRALAkDLNLIAADNFGRAAAKQQVKEIIYVRGSQFDE-----------ETVKQLGAYGVPI 130
Cdd:cd05245   72 -HSMGSGGDFE-EADRRAARNFARAARAAGVKRIIYLGGLIPKGeelsphlrsraEVGEILRAGGVPV 137

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504427501   5 VLLAGGTGYIGKSLIKEL-----------RDTTTLhtisqypKSQSHADTTVIKGDIYHYADVLRAMEGMDiAVYFLDPT 73
Cdd:COG0702    2 ILVTGATGFIGRRVVRALlarghpvralvRDPEKA-------AALAAAGVEVVQGDLDDPESLAAALAGVD-AVFLLVPS 73

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 504427501  74 KHSAKLTRALAkdlnliAADNFGRAAAKQQVKEIIYV 110
Cdd:COG0702   74 GPGGDFAVDVE------GARNLADAAKAAGVKRIVYL 104

3beta-hydroxysteroid dehydrogenases (3b-HSD)-like, extended (e) SDRs; Extended SDR family domains belonging to this subgroup have the characteristic active site tetrad and a fairly well-conserved NAD(P)-binding motif. 3b-HSD catalyzes the NAD-dependent conversion of various steroids, such as pregnenolone to progesterone, or androstenediol to testosterone. This subgroup includes an unusual bifunctional 3b-HSD/C-4 decarboxylase from Arabidopsis thaliana, and Saccharomyces cerevisiae ERG26, a 3b-HSD/C-4 decarboxylase, involved in the synthesis of ergosterol, the major sterol of yeast. It also includes human 3 beta-HSD/HSD3B1 and C(27) 3beta-HSD/ [3beta-hydroxy-delta(5)-C(27)-steroid oxidoreductase; HSD3B7]. C(27) 3beta-HSD/HSD3B7 is a membrane-bound enzyme of the endoplasmic reticulum, that catalyzes the isomerization and oxidation of 7alpha-hydroxylated sterol intermediates, an early step in bile acid biosynthesis. Mutations in the human NSDHL (NAD(P)H steroid dehydrogenase-like protein) cause CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects), an X-linked dominant, male-lethal trait. Mutations in the human gene encoding C(27) 3beta-HSD underlie a rare autosomal recessive form of neonatal cholestasis. 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 sythase 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 504427501   5 VLLAGGTGYIGKSLIKELRDTTTLHTIS-------QYPKSQSHADTTVIKGDIYHYADVLRAMEGMDIAVYFLDPTkHSA 77
Cdd:cd05241    2 VLVTGGSGFFGERLVKQLLERGGTYVRSfdiappgEALSAWQHPNIEFLKGDITDRNDVEQALSGADCVFHTAAIV-PLA 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 504427501  78 KLtRALAKDLNLIAADNFGRAAAKQQVKEIIY 109
Cdd:cd05241   81 GP-RDLYWEVNVGGTQNVLDACQRCGVQKFVY 111

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 504427501   5 VLLAGGTGYIGKSLIKELRDTTtlHTI-------SQYPKsQSHADTTVIKGDIYHYADVLRAMEGMDIAVYfldpTKHSA 77
Cdd:cd05243    2 VLVVGATGKVGRHVVRELLDRG--YQVralvrdpSQAEK-LEAAGAEVVVGDLTDAESLAAALEGIDAVIS----AAGSG 74

                         90       100       110
                 ....*....|....*....|....*....|...
gi 504427501  78 KLTRALAKDLNLIAADNFGRAAAKQQVKEIIYV 110
Cdd:cd05243   75 GKGGPRTEAVDYDGNINLIDAAKKAGVKRFVLV 107

3beta-hydroxysteroid dehydrogenase (3b-HSD)-like, subgroup1, extended (e) SDRs; An uncharacterized subgroup of the 3b-HSD-like extended-SDR family. Proteins in this subgroup have the characteristic active site tetrad and NAD(P)-binding motif of extended-SDRs. 3 beta-HSD catalyzes the oxidative conversion of delta 5-3 beta-hydroxysteroids to the delta 4-3-keto configuration; this activity is essential for the biosynthesis of all classes of hormonal steroids. 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 sythase 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 504427501   5 VLLAGGTGYIGKSLIKELRDTTT---LHTISQyPKSQSHADTTVIKGDIYHYADVLRAMEGMD----IAVYFLDPTKhsa 77
Cdd:cd09812    2 VLITGGGGYFGFRLGCALAKSGVhviLFDIRR-PQQELPEGIKFIQADVRDLSQLEKAVAGVDcvfhIASYGMSGRE--- 77

                         90       100       110
                 ....*....|....*....|....*....|..
gi 504427501  78 KLTRALAKDLNLIAADNFGRAAAKQQVKEIIY 109
Cdd:cd09812   78 QLNRELIEEINVRGTENIIQVCVRRRVPRLIY 109

UDP-Glcnac (UDP-linked N-acetylglucosamine) inverting 4,6-dehydratase, extended (e) SDRs; UDP-Glcnac inverting 4,6-dehydratase was identified in Helicobacter pylori as the hexameric flaA1 gene product (FlaA1). FlaA1 is hexameric, possesses UDP-GlcNAc-inverting 4,6-dehydratase activity, and catalyzes the first step in the creation of a pseudaminic acid derivative in protein glycosylation. Although this subgroup has the NADP-binding motif characteristic of extended SDRs, its members tend to have a Met substituted for the active site Tyr found in most SDR families. 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 504427501   5 VLLAGGTGYIGKSLIKEL------------RDTTTLHTISQ-YPKSQSHADTTVIKGDIYHYADVLRAME--GMDIaVYF 69
Cdd:cd05237    5 ILVTGGAGSIGSELVRQIlkfgpkklivfdRDENKLHELVReLRSRFPHDKLRFIIGDVRDKERLRRAFKerGPDI-VFH 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 504427501  70 LDPTKH--SAKL--TRALakDLNLIAADNFGRAAAKQQVKEIIYV 110
Cdd:cd05237   84 AAALKHvpSMEDnpEEAI--KTNVLGTKNVIDAAIENGVEKFVCI 126

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 504427501   5 VLLAGGTGYIGKSLIKEL-----------RDTTTLHTISQYPKSQSHadttvikGDIYHYADVLRAMEGMDiAVYFLDPT 73
Cdd:cd05226    1 ILILGATGFIGRALARELleqghevtllvRNTKRLSKEDQEPVAVVE-------GDLRDLDSLSDAVQGVD-VVIHLAGA 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 504427501  74 KHSAKLTRalakDLNLIAADNFGRAAAKQQVKEIIYVRGsqfdeetvkqLGAYGVPIRTTE 134
Cdd:cd05226   73 PRDTRDFC----EVDVEGTRNVLEAAKEAGVKHFIFISS----------LGAYGDLHEETE 119