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 2217351526   5 DGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKYPGIQTRVLDVTKKKQIDQFANEVERLDVLFNVAGF 84
Cdd:cd05368     1 DGKVALITAAAQGIGRAIALAFAREGANVIATDINEEKLKELERGPGITTRVLDVTDKEQVAALAKEEGRIDVLFNCAGF 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217351526  85 VHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSVKG 140
Cdd:cd05368    81 VHHGSILDCEDDDWDFAMNLNVRSMYLMIKAVLPKMLARKDGSIINMSSVASSIKG 136

human DHRS6-like, classical (c) SDRs; Human DHRS6, and similar proteins. These proteins are classical SDRs, with a canonical active site tetrad and a close match to the typical Gly-rich NAD-binding motif. Human DHRS6 is a cytosolic type 2 (R)-hydroxybutyrate dehydrogenase, which catalyses the conversion of (R)-hydroxybutyrate to acetoacetate. Also included in this subgroup is Escherichia coli UcpA (upstream cys P). 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. Note: removed : needed to make this chiodl smaller when drew final trees: rmeoved text form description: Other proteins in this subgroup include Thermoplasma acidophilum aldohexose dehydrogenase, which has high dehydrogenase activity against D-mannose, Bacillus subtilis BacC involved in the biosynthesis of the dipeptide bacilysin and its antibiotic moiety anticapsin, Sphingomonas paucimobilis strain B90 LinC, involved in the degradation of hexachlorocyclohexane isomers...... P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   5 DGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKYPGIQTRVLDVTKKKQIDQFANEVERLDVLFNVAGF 84
Cdd:cd05368     1 DGKVALITAAAQGIGRAIALAFAREGANVIATDINEEKLKELERGPGITTRVLDVTDKEQVAALAKEEGRIDVLFNCAGF 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217351526  85 VHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSVKG 140
Cdd:cd05368    81 VHHGSILDCEDDDWDFAMNLNVRSMYLMIKAVLPKMLARKDGSIINMSSVASSIKG 136

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  25 AFAREGAKVIATDINE---SKLQELEKYPGIQTRVLDVTKKKQIDQFANEVE----RLDVLFNVAGFV--HHGTVLDCEE 95
Cdd:pfam13561  15 ALAEEGAEVVLTDLNEalaKRVEELAEELGAAVLPCDVTDEEQVEALVAAAVekfgRLDILVNNAGFApkLKGPFLDTSR 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2217351526  96 KDWDFSMNLNVRSMYLMIKAFLPKMlaQKSGNIINMSSVASSV 138
Cdd:pfam13561  95 EDFDRALDVNLYSLFLLAKAALPLM--KEGGSIVNLSSIGAER 135

3-oxoacyl-(acyl-carrier-protein) reductase; This model represents 3-oxoacyl-[ACP] reductase, also called 3-ketoacyl-acyl carrier protein reductase, an enzyme of fatty acid biosynthesis. [Fatty acid and phospholipid metabolism, Biosynthesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  24 LAFAREGAKVIATDINESKL-----QELEKYPG-IQTRVLDVTKKKQIDQFANEVE----RLDVLFNVAGFVHHGTVLDC 93
Cdd:TIGR01830  16 LKLAKEGAKVIITYRSSEEGaeevvEELKALGVkALGVVLDVSDREDVKAVVEEIEeelgTIDILVNNAGITRDNLLMRM 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2217351526  94 EEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVA 135
Cdd:TIGR01830  96 KEEDWDAVIDTNLTGVFNLTQAVLRIMIKQRSGRIINISSVV 137

human DHRS6-like, classical (c) SDRs; Human DHRS6, and similar proteins. These proteins are classical SDRs, with a canonical active site tetrad and a close match to the typical Gly-rich NAD-binding motif. Human DHRS6 is a cytosolic type 2 (R)-hydroxybutyrate dehydrogenase, which catalyses the conversion of (R)-hydroxybutyrate to acetoacetate. Also included in this subgroup is Escherichia coli UcpA (upstream cys P). 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. Note: removed : needed to make this chiodl smaller when drew final trees: rmeoved text form description: Other proteins in this subgroup include Thermoplasma acidophilum aldohexose dehydrogenase, which has high dehydrogenase activity against D-mannose, Bacillus subtilis BacC involved in the biosynthesis of the dipeptide bacilysin and its antibiotic moiety anticapsin, Sphingomonas paucimobilis strain B90 LinC, involved in the degradation of hexachlorocyclohexane isomers...... P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   5 DGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKYPGIQTRVLDVTKKKQIDQFANEVERLDVLFNVAGF 84
Cdd:cd05368     1 DGKVALITAAAQGIGRAIALAFAREGANVIATDINEEKLKELERGPGITTRVLDVTDKEQVAALAKEEGRIDVLFNCAGF 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217351526  85 VHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSVKG 140
Cdd:cd05368    81 VHHGSILDCEDDDWDFAMNLNVRSMYLMIKAVLPKMLARKDGSIINMSSVASSIKG 136

NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and metabolism]; NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family is part of the Pathway/BioSystem: Fatty acid biosynthesis

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   1 MGRLDGKVIILTaaaqgigqaaaLAFAREGAKVIATDINESKLQ----ELEKYPG-IQTRVLDVTKKKQIDQFANEVE-- 73
Cdd:COG1028     1 MTRLKGKVALVTggssgigraiaRALAAEGARVVITDRDAEALEaaaaELRAAGGrALAVAADVTDEAAVEALVAAAVaa 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217351526  74 --RLDVLFNVAGFVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSV 138
Cdd:COG1028    81 fgRLDILVNNAGITPPGPLEELTEEDWDRVLDVNLKGPFLLTRAALPHMRERGGGRIVNISSIAGLR 147

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  24 LAFAREGAKVIATDINESKLQEL-----EKYPGIQTRVLDVTKKKQIDQFANEVE----RLDVLFNVAGFVHHGTVLDCE 94
Cdd:COG0300    23 RALAARGARVVLVARDAERLEALaaelrAAGARVEVVALDVTDPDAVAALAEAVLarfgPIDVLVNNAGVGGGGPFEELD 102

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2217351526  95 EKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSV 138
Cdd:COG0300   103 LEDLRRVFEVNVFGPVRLTRALLPLMRARGRGRIVNVSSVAGLR 146

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  24 LAFAREGAKVIATDINESKLQEL-----EKYPGIQTRVLDVTKKKQIDQFANEVE----RLDVLFNVAGFVHHGTVLDCE 94
Cdd:pfam00106  18 KRLAKEGAKVVLVDRSEEKLEAVakelgALGGKALFIQGDVTDRAQVKALVEQAVerlgRLDILVNNAGITGLGPFSELS 97

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  95 EKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVA-----------SSVKGGSVSF-RGLRCSY 152
Cdd:pfam00106  98 DEDWERVIDVNLTGVFNLTRAVLPAMIKGSGGRIVNISSVAglvpypggsaySASKAAVIGFtRSLALEL 167

beta-Keto acyl carrier protein reductase (BKR), involved in Type II FAS, classical (c) SDRs; This subgroup includes the Escherichai coli K12 BKR, FabG. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet) 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: TGxxxGxG in classical SDRs. 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 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. 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-151 and Lys-155, and well as Asn-111 (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 2217351526  24 LAFAREGAKVIATDINESKLQELE---KYPGIQTRVL--DVTKKKQIDQFANEVE----RLDVLFNVAGFVHHGTVLDCE 94
Cdd:cd05333    18 LRLAAEGAKVAVTDRSEEAAAETVeeiKALGGNAAALeaDVSDREAVEALVEKVEaefgPVDILVNNAGITRDNLLMRMS 97

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2217351526  95 EKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSV 134
Cdd:cd05333    98 EEDWDAVINVNLTGVFNVTQAVIRAMIKRRSGRIINISSV 137

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  24 LAFAREGAKVIATDINESKLQELEKYPGIQTRV--LDVTKKKQIDQFANEVE----RLDVLFNVAGFVHHGTVLDCEEKD 97
Cdd:cd05374    18 LALAAQGYRVIATARNPDKLESLGELLNDNLEVleLDVTDEESIKAAVKEVIerfgRIDVLVNNAGYGLFGPLEETSIEE 97

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2217351526  98 WDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSVkggSVSFRGLRCS 151
Cdd:cd05374    98 VRELFEVNVFGPLRVTRAFLPLMRKQGSGRIVNVSSVAGLV---PTPFLGPYCA 148

3-oxoacyl-ACP reductase FabG;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  23 ALAFAREGAKVIATDINESKLQELE---KYPGIQTRVL--DVTKKKQ----IDQFANEVERLDVLFNVAGFVHHGTVLDC 93
Cdd:PRK05653   22 ALRLAADGAKVVIYDSNEEAAEALAaelRAAGGEARVLvfDVSDEAAvralIEAAVEAFGALDILVNNAGITRDALLPRM 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217351526  94 EEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVAssvkgGSVSFRGL 148
Cdd:PRK05653  102 SEEDWDRVIDVNLTGTFNVVRAALPPMIKARYGRIVNISSVS-----GVTGNPGQ 151

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   1 MGRLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQEL-EKYPGIQ--TRVLDVTKKKQIDQ-FANEVER-- 74
Cdd:PRK12829    6 LKPLDGLRVLVTGGASGIGRAIAEAFAEAGARVHVCDVSEAALAATaARLPGAKvtATVADVADPAQVERvFDTAVERfg 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217351526  75 -LDVLFNVAG-FVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGN-IINMSSVA 135
Cdd:PRK12829   86 gLDVLVNNAGiAGPTGGIDEITPEQWEQTLAVNLNGQFYFARAAVPLLKASGHGGvIIALSSVA 149

2,3-dihydroxybenzoate-2,3-dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   1 MGRLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESklqELEKYPgIQTRVLDVTKKKQID----QFANEVERLD 76
Cdd:PRK08220    3 AMDFSGKTVWVTGAAQGIGYAVALAFVEAGAKVIGFDQAFL---TQEDYP-FATFVLDVSDAAAVAqvcqRLLAETGPLD 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217351526  77 VLFNVAGFVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSV 138
Cdd:PRK08220   79 VLVNAAGILRMGATDSLSDEDWQQTFAVNAGGAFNLFRAVMPQFRRQRSGAIVTVGSNAAHV 140

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   1 MGRLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELE---KYPGIQ--TRVLDVTKKKQIDQFANEVE-- 73
Cdd:PRK12939    2 ASNLAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAaalEAAGGRahAIAADLADPASVQRFFDAAAaa 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217351526  74 --RLDVLFNVAGFVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSS 133
Cdd:PRK12939   82 lgGLDGLVNNAGITNSKSATELDIDTWDAVMNVNVRGTFLMLRAALPHLRDSGRGRIVNLAS 143

3-oxoacyl-(acyl-carrier-protein) reductase; This model represents 3-oxoacyl-[ACP] reductase, also called 3-ketoacyl-acyl carrier protein reductase, an enzyme of fatty acid biosynthesis. [Fatty acid and phospholipid metabolism, Biosynthesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  24 LAFAREGAKVIATDINESKL-----QELEKYPG-IQTRVLDVTKKKQIDQFANEVE----RLDVLFNVAGFVHHGTVLDC 93
Cdd:TIGR01830  16 LKLAKEGAKVIITYRSSEEGaeevvEELKALGVkALGVVLDVSDREDVKAVVEEIEeelgTIDILVNNAGITRDNLLMRM 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2217351526  94 EEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVA 135
Cdd:TIGR01830  96 KEEDWDAVIDTNLTGVFNLTQAVLRIMIKQRSGRIINISSVV 137

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  26 FAREGAKVIATDINESKLQEL-----EKYPGIQTRVLDVTKKKQIDQFANEVER----LDVLFNVAGFVHHGTVLDCEEK 96
Cdd:cd05339    19 FAKRGAKVVILDINEKGAEETannvrKAGGKVHYYKCDVSKREEVYEAAKKIKKevgdVTILINNAGVVSGKKLLELPDE 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2217351526  97 DWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVAS 136
Cdd:cd05339    99 EIEKTFEVNTLAHFWTTKAFLPDMLERNHGHIVTIASVAG 138

SDR family oxidoreductase UcpA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   1 MGRLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINES--KLQELEKYPGIQ--TRVLDVTKKKQIDQFANEVE--- 73
Cdd:PRK08226    1 MGKLTGKTALITGALQGIGEGIARVFARHGANLILLDISPEieKLADELCGRGHRctAVVADVRDPASVAAAIKRAKeke 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217351526  74 -RLDVLFNVAGFVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSV 134
Cdd:PRK08226   81 gRIDILVNNAGVCRLGSFLDMSDEDRDFHIDINIKGVWNVTKAVLPEMIARKDGRIVMMSSV 142

aldose dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   1 MGRLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINEsklQELEKYPGIQtrvLDVTKKKQ----IDQFANEVERLD 76
Cdd:PRK06398    1 DLGLKDKVAIVTGGSQGIGKAVVNRLKEEGSNVINFDIKE---PSYNDVDYFK---VDVSNKEQvikgIDYVISKYGRID 74

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217351526  77 VLFNVAGFVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSV 138
Cdd:PRK06398   75 ILVNNAGIESYGAIHAVEEDEWDRIINVNVNGIFLMSKYTIPYMLKQDKGVIINIASVQSFA 136

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   3 RLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKYPGIQTRVL----DVTKKKQIDQFANE-VE---R 74
Cdd:PRK07231    2 RLEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILAGGRAIavaaDVSDEADVEAAVAAaLErfgS 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217351526  75 LDVLFNVAGFVH-HGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVA 135
Cdd:PRK07231   82 VDILVNNAGTTHrNGPLLDVDEAEFDRIFAVNVKSPYLWTQAAVPAMRGEGGGAIVNVASTA 143

3beta17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; This subgroup includes members identified as 3beta17beta hydroxysteroid dehydrogenase, 20beta hydroxysteroid dehydrogenase, and R-alcohol dehydrogenase. These proteins exhibit the canonical active site tetrad and glycine rich NAD(P)-binding motif of the classical SDRs. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. 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 2217351526   2 GRLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKYPGIQTRV--LDVTK----KKQIDQFANEVERL 75
Cdd:cd05341     1 NRLKGKVAIVTGGARGLGLAHARLLVAEGAKVVLSDILDEEGQAAAAELGDAARFfhLDVTDedgwTAVVDTAREAFGRL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217351526  76 DVLFNVAGFVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSV 138
Cdd:cd05341    81 DVLVNNAGILTGGTVETTTLEEWRRLLDINLTGVFLGTRAVIPPMKEAGGGSIINMSSIEGLV 143

clavulanic acid dehydrogenase (CAD), classical (c) SDR; CAD catalyzes the NADP-dependent reduction of clavulanate-9-aldehyde to clavulanic acid, a beta-lactamase inhibitor. 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 2217351526   4 LDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKY---PGIQTRVL--DVTKKKQIDQFAN----EVER 74
Cdd:cd08934     1 LQGKVALVTGASSGIGEATARALAAEGAAVAIAARRVDRLEALADEleaEGGKALVLelDVTDEQQVDAAVErtveALGR 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217351526  75 LDVLFNVAGFVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSVKG 140
Cdd:cd08934    81 LDILVNNAGIMLLGPVEDADTTDWTRMIDTNLLGLMYTTHAALPHHLLRNKGTIVNISSVAGRVAV 146

secoisolariciresinol dehydrogenase (secoisolariciresinol-DH)-like, classical (c) SDRs; Podophyllum secoisolariciresinol-DH is a homo tetrameric, classical SDR that catalyzes the NAD-dependent conversion of (-)-secoisolariciresinol to (-)-matairesinol via a (-)-lactol intermediate. (-)-Matairesinol is an intermediate to various 8'-lignans, including the cancer-preventive mammalian lignan, and those involved in vascular plant defense. This subgroup also includes rice momilactone A synthase which catalyzes the conversion of 3beta-hydroxy-9betaH-pimara-7,15-dien-19,6beta-olide into momilactone A, Arabidopsis ABA2 which during abscisic acid (ABA) biosynthesis, catalyzes the conversion of xanthoxin to abscisic aldehyde and, maize Tasselseed2 which participate in the maize sex determination pathway. 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, 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 2217351526   3 RLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKYPGIQTRVL---DVTKKkqiDQFANEVE------ 73
Cdd:cd05326     1 RLDGKVAIITGGASGIGEATARLFAKHGARVVIADIDDDAGQAVAAELGDPDISFvhcDVTVE---ADVRAAVDtavarf 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217351526  74 -RLDVLFNVAGFV--HHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASSVKGG 141
Cdd:cd05326    78 gRLDIMFNNAGVLgaPCYSILETSLEEFERVLDVNVYGAFLGTKHAARVMIPAKKGSIVSVASVAGVVGGL 148

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  24 LAFAREGAKVIATDINESKLQELEKY---PGIQTRVL--DVTKKKQIDQFANEVER----LDVLFNVAGFVHHGTVLDCE 94
Cdd:PRK05650   18 LRWAREGWRLALADVNEEGGEETLKLlreAGGDGFYQrcDVRDYSQLTALAQACEEkwggIDVIVNNAGVASGGFFEELS 97

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2217351526  95 EKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVA 135
Cdd:PRK05650   98 LEDWDWQIAINLMGVVKGCKAFLPLFKRQKSGRIVNIASMA 138

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526  25 AFAREGAKVIATDINESKLQELEKYPGIQTRV------LDVTKKKQIDQFAN----EVERLDVLFNVAGFVHhGT--VLD 92
Cdd:cd05346    19 RFAKAGAKLILTGRRAERLQELADELGAKFPVkvlplqLDVSDRESIEAALEnlpeEFRDIDILVNNAGLAL-GLdpAQE 97

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217351526  93 CEEKDWDFSMNLNVRSMYLMIKAFLPKMLAQKSGNIINMSSVASS--VKGGSV 143
Cdd:cd05346    98 ADLEDWETMIDTNVKGLLNVTRLILPIMIARNQGHIINLGSIAGRypYAGGNV 150

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351526   1 MGRLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKYPG-----IQTRVLDVTKKKQI-DQFANEVER 74
Cdd:PRK06500    1 MSRLQGKTALITGGTSGIGLETARQFLAEGARVAITGRDPASLEAARAELGesalvIRADAGDVAAQKALaQALAEAFGR 80