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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578800093  53 QLAREFAERGArKIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREKVSQP 117
Cdd:cd05339   14 LLALEFAKRGA-KVVILDINEKGAEETANNVRKAGGKVHYYKCDVSKREEVYEAAKKIKKEVGDV 77

human 17-beta-hydroxysteroid dehydrogenase XI-like, classical (c) SDRs; 17-beta-hydroxysteroid dehydrogenases (17betaHSD) are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 17betaHSD type XI, a classical SDR, preferentially converts 3alpha-Adiol to androsterone but not numerous other tested steroids. This subgroup of classical SDRs also includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578800093  53 QLAREFAERGArKIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREKVSQP 117
Cdd:cd05339   14 LLALEFAKRGA-KVVILDINEKGAEETANNVRKAGGKVHYYKCDVSKREEVYEAAKKIKKEVGDV 77

KR domain; This enzymatic domain is part of bacterial polyketide synthases and catalyzes 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578800093   48 RGIGRQLAREFAERGARKIVLWGRTEKCL---KETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREK 113
Cdd:pfam08659  10 GGLGRELARWLAERGARHLVLLSRSAAPRpdaQALIAELEARGVEVVVVACDVSDPDAVAALLAEIKAE 78

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578800093    47 GRGIGRQLAREFAERGARKIVLWGRT---EKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREK 113
Cdd:smart00822   9 LGGLGRALARWLAERGARRLVLLSRSgpdAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAAIPAV 78

human 17-beta-hydroxysteroid dehydrogenase XI-like, classical (c) SDRs; 17-beta-hydroxysteroid dehydrogenases (17betaHSD) are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 17betaHSD type XI, a classical SDR, preferentially converts 3alpha-Adiol to androsterone but not numerous other tested steroids. This subgroup of classical SDRs also includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578800093  53 QLAREFAERGArKIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREKVSQP 117
Cdd:cd05339   14 LLALEFAKRGA-KVVILDINEKGAEETANNVRKAGGKVHYYKCDVSKREEVYEAAKKIKKEVGDV 77

classical (c) SDR, subgroup 3; These proteins are members of the classical SDR family, with a canonical active site triad (and also 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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 578800093  55 AREFAERGArKIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTA 107
Cdd:cd05360   17 ALAFAERGA-KVVLAARSAEALHELAREVRELGGEAIAVVADVADAAQVERAA 68

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)-like, classical (c) SDRs; Human 11beta_HSD1 catalyzes the NADP(H)-dependent interconversion of cortisone and cortisol. This subgroup also includes human dehydrogenase/reductase SDR family member 7C (DHRS7C) and DHRS7B. These proteins have the GxxxGxG nucleotide binding motif and S-Y-K catalytic triad characteristic of the SDRs, but have an atypical C-terminal domain that contributes to homodimerization contacts. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578800093  53 QLAREFAERGARkIVLWGRTEKCLKETTEEIRQMG-TECHYFICDVGNREEVYQTAKAVREKVSQ 116
Cdd:cd05332   18 ELAYHLARLGAR-LVLSARREERLEEVKSECLELGaPSPHVVPLDMSDLEDAEQVVEEALKLFGG 81

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578800093  47 GRGIGRQLAREFAERGARkIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREK 113
Cdd:COG0300   14 SSGIGRALARALAARGAR-VVLVARDAERLEALAAELRAAGARVEVVALDVTDPDAVAALAEAVLAR 79

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578800093  47 GRGIGRQLAREFAERGArKIVLWGRTEKCLKETTEEIR----QMGTECHYFICDVGNREEVYQTAKAVREKVSQP 117
Cdd:cd08939   10 SSGIGKALAKELVKEGA-NVIIVARSESKLEEAVEEIEaeanASGQKVSYISADLSDYEEVEQAFAQAVEKGGPP 83

hypothetical protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578800093  56 REFAERGAR---KIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREKVSQP 117
Cdd:PRK06194  20 LAFARIGAAlgmKLVLADVQQDALDRAVAELRAQGAEVLGVRTDVSDAAQVEALADAALERFGAV 84

SDR family oxidoreductase;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 578800093  55 AREFAERGARkiVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREK 113
Cdd:PRK08589  23 AIALAQEGAY--VLAVDIAEAVSETVDKIKSNGGKAKAYHVDISDEQQVKDFASEIKEQ 79

Enoyl-(Acyl carrier protein) reductase; This domain is found in Enoyl-(Acyl carrier protein) reductases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 578800093   55 AREFAERGARkIVLWGRTEKCLKETTEEIRQMGTEchYFICDVGNREEVYQTAKAVREK 113
Cdd:pfam13561  13 ARALAEEGAE-VVLTDLNEALAKRVEELAEELGAA--VLPCDVTDEEQVEALVAAAVEK 68

SDR family oxidoreductase;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 578800093  55 AREFAERGARkIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVRE 112
Cdd:PRK06139  24 AEAFARRGAR-LVLAARDEEALQAVAEECRALGAEVLVVPTDVTDADQVKALATQAAS 80

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578800093  35 DLSRENVLITGGGRGIGRQLAREFAERGARkIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEV 103
Cdd:PRK05653   2 SLQGKTALVTGASRGIGRAIALRLAADGAK-VVIYDSNEEAAEALAAELRAAGGEARVLVFDVSDEAAV 69

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578800093    47 GRGIGRQLAREFAERGARKIVLWGRT---EKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREK 113
Cdd:smart00822   9 LGGLGRALARWLAERGARRLVLLSRSgpdAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAAIPAV 78

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578800093  36 LSRENVLITGGGRGIGRQLAREFAERGARKIVLWGRTEKclkeTTEEIRQMGTEChyFICDVGNREEVYQTAKAVREK 113
Cdd:PRK06463   5 FKGKVALITGGTRGIGRAIAEAFLREGAKVAVLYNSAEN----EAKELREKGVFT--IKCDVGNRDQVKKSKEVVEKE 76

ketoreductase (KR), subgroup 2, complex (x) SDRs; Ketoreductase, a module of the multidomain polyketide synthase (PKS), has 2 subdomains, each corresponding to a SDR family monomer. The C-terminal subdomain catalyzes the NADPH-dependent reduction of the beta-carbonyl of a polyketide to a hydroxyl group, a step in the biosynthesis of polyketides, such as erythromycin. The N-terminal subdomain, an interdomain linker, is a truncated Rossmann fold which acts to stabilizes the catalytic subdomain. Unlike typical SDRs, the isolated domain does not oligomerize but is composed of 2 subdomains, each resembling an SDR monomer. The active site resembles that of typical SDRs, except that the usual positions of the catalytic Asn and Tyr are swapped, so that the canonical YXXXK motif changes to YXXXN. Modular PKSs are multifunctional structures in which the makeup recapitulates that found in (and may have evolved from) FAS. Polyketide synthesis also proceeds via the addition of 2-carbon units as in fatty acid synthesis. The complex SDR NADP-binding motif, GGXGXXG, is often present, but is not strictly conserved in each instance of the module. This subfamily includes both KR domains of the Bacillus subtilis Pks J,-L, and PksM, and all three KR domains of PksN, components of the megacomplex bacillaene synthase, which synthesizes the antibiotic bacillaene. 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 KRs have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578800093  48 RGIGRQLAREFAERGARKIVLWGRTEKCLKE-----TTEEIRQMGTECHYFICDVGNREEVYQTAKAVREK 113
Cdd:cd08953  215 GGIGRALARALARRYGARLVLLGRSPLPPEEewkaqTLAALEALGARVLYISADVTDAAAVRRLLEKVRER 285

ketoreductase (KR) and fatty acid synthase (FAS), complex (x) SDRs; Ketoreductase, a module of the multidomain polyketide synthase (PKS), has 2 subdomains, each corresponding to a SDR family monomer. The C-terminal subdomain catalyzes the NADPH-dependent reduction of the beta-carbonyl of a polyketide to a hydroxyl group, a step in the biosynthesis of polyketides, such as erythromycin. The N-terminal subdomain, an interdomain linker, is a truncated Rossmann fold which acts to stabilizes the catalytic subdomain. Unlike typical SDRs, the isolated domain does not oligomerize but is composed of 2 subdomains, each resembling an SDR monomer. The active site resembles that of typical SDRs, except that the usual positions of the catalytic Asn and Tyr are swapped, so that the canonical YXXXK motif changes to YXXXN. Modular PKSs are multifunctional structures in which the makeup recapitulates that found in (and may have evolved from) FAS. In some instances, such as porcine FAS, an enoyl reductase (ER) module is inserted between the sub-domains. Fatty acid synthesis occurs via the stepwise elongation of a chain (which is attached to acyl carrier protein, ACP) with 2-carbon units. Eukaryotic systems consist of large, multifunctional synthases (type I) while bacterial, type II systems, use single function proteins. Fungal fatty acid synthase uses a dodecamer of 6 alpha and 6 beta subunits. In mammalian type FAS cycles, ketoacyl synthase forms acetoacetyl-ACP which is reduced by the NADP-dependent beta-KR, forming beta-hydroxyacyl-ACP, which is in turn dehydrated by dehydratase to a beta-enoyl intermediate, which is reduced by NADP-dependent beta-ER. Polyketide synthesis also proceeds via the addition of 2-carbon units as in fatty acid synthesis. The complex SDR NADP-binding motif, GGXGXXG, is often present, but is not strictly conserved in each instance of the module. 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 KRs have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578800093  53 QLAREFAERGARKIVLWGRTEKCLKETTEEI--RQMGTECHYFICDVGNREEVYQTAKAVREkvSQPLS 119
Cdd:cd05274  165 LVARWLAARGARHLVLLSRRGPAPRAAARAAllRAGGARVSVVRCDVTDPAALAALLAELAA--GGPLA 231

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578800093  35 DLSRENVLITGGGRGIGRQLAREFAERGARKIVLwGRTEKCLKETTEEIRQMgtecHYFICDVGNREEVYQTAKAV 110
Cdd:cd05370    2 KLTGNTVLITGGTSGIGLALARKFLEAGNTVIIT-GRREERLAEAKKELPNI----HTIVLDVGDAESVEALAEAL 72

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

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578800093  35 DLSRENVLITGGGRGIGRQLAREFAERGArKIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREKV 114
Cdd:cd05347    2 SLKGKVALVTGASRGIGFGIASGLAEAGA-NIVINSRNEEKAEEAQQLIEKEGVEATAFTCDVSDEEAIKAAVEAIEEDF 80

                 ..
gi 578800093 115 SQ 116
Cdd:cd05347   81 GK 82

short chain dehydrogenase; Provisional

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578800093  47 GRGIGRQLAREFAERGARkIVLWGRTEKCLKETTEEIRQMGTECHYFICDVGNREEVYQTAKAVREKVSQ 116
Cdd:PRK07677  10 SSGMGKAMAKRFAEEGAN-VVITGRTKEKLEEAKLEIEQFPGQVLTVQMDVRNPEDVQKMVEQIDEKFGR 78