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 193203119   3 KTVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYALKKD-VKTTVVCP 81
Cdd:cd05339  102 KTFEVNTLAHFWTTKAFLPDMLERNHGHIVTIASVAGLISPAGLADYCASKAAAVGFHESLRLELKAYGKPgIKTTLVCP 181

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 193203119  82 IYINTGMFDGIATKWPTLLPILSPEYVVDCIMEAVLTDRAFLAIPKFSYIFIALAGLLPTEV 143
Cdd:cd05339  182 YFINTGMFQGVKTPRPLLAPILEPEYVAEKIVRAILTNQQMLYLPFYAYFLPILKRTLPTPV 243

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 193203119   3 KTVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYALKKD-VKTTVVCP 81
Cdd:cd05339  102 KTFEVNTLAHFWTTKAFLPDMLERNHGHIVTIASVAGLISPAGLADYCASKAAAVGFHESLRLELKAYGKPgIKTTLVCP 181

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 193203119  82 IYINTGMFDGIATKWPTLLPILSPEYVVDCIMEAVLTDRAFLAIPKFSYIFIALAGLLPTEV 143
Cdd:cd05339  182 YFINTGMFQGVKTPRPLLAPILEPEYVAEKIVRAILTNQQMLYLPFYAYFLPILKRTLPTPV 243

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   4 TVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYAlkKDVKTTVVCPIY 83
Cdd:PRK07825 105 ILDVNVYGVILGSKLAAPRMVPRGRGHVVNVASLAGKIPVPGMATYCASKHAVVGFTDAARLELRG--TGVHVSVVLPSF 182

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 193203119  84 INTGMFDGiaTKWPTLLPILSPEYVVDCIMEAVLTDRAFLAIPKFSYIFIALAGLLPTEVLN 145
Cdd:PRK07825 183 VNTELIAG--TGGAKGFKNVEPEDVAAAIVGTVAKPRPEVRVPRALGPLAQAQRLLPRRVRE 242

3-hydroxybutyrate dehydrogenase; This model represents a subfamily of the short chain dehydrogenases. Characterized members so far as 3-hydroxybutyrate dehydrogenases and are found in species that accumulate ester polmers called polyhydroxyalkanoic acids (PHAs) under certain conditions. Several members of the family are from species not known to accumulate PHAs, including Oceanobacillus iheyensis and Bacillus subtilis. However, polymer formation is not required for there be a role for 3-hydroxybutyrate dehydrogenase; it may be members of this family have the same function in those species.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119    5 VSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYAlkKDVKTTVVCPIYI 84
Cdd:TIGR01963 106 IAVMLTSAFHTIRAALPHMKKQGWGRIINIASAHGLVASPFKSAYVAAKHGLIGLTKVLALEVAE--HGITVNAICPGYV 183

                  ..
gi 193203119   85 NT 86
Cdd:TIGR01963 184 RT 185

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 193203119   3 KTVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYALKKD-VKTTVVCP 81
Cdd:cd05339  102 KTFEVNTLAHFWTTKAFLPDMLERNHGHIVTIASVAGLISPAGLADYCASKAAAVGFHESLRLELKAYGKPgIKTTLVCP 181

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 193203119  82 IYINTGMFDGIATKWPTLLPILSPEYVVDCIMEAVLTDRAFLAIPKFSYIFIALAGLLPTEV 143
Cdd:cd05339  182 YFINTGMFQGVKTPRPLLAPILEPEYVAEKIVRAILTNQQMLYLPFYAYFLPILKRTLPTPV 243

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   4 TVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYAlkKDVKTTVVCPIY 83
Cdd:PRK07825 105 ILDVNVYGVILGSKLAAPRMVPRGRGHVVNVASLAGKIPVPGMATYCASKHAVVGFTDAARLELRG--TGVHVSVVLPSF 182

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 193203119  84 INTGMFDGiaTKWPTLLPILSPEYVVDCIMEAVLTDRAFLAIPKFSYIFIALAGLLPTEVLN 145
Cdd:PRK07825 183 VNTELIAG--TGGAKGFKNVEPEDVAAAIVGTVAKPRPEVRVPRALGPLAQAQRLLPRRVRE 242

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119    3 KTVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYalKKDVKTTVVCPI 82
Cdd:pfam00106 103 RVIDVNLTGVFNLTRAVLPAMIKGSGGRIVNISSVAGLVPYPGGSAYSASKAAVIGFTRSLALELA--PHGIRVNAVAPG 180

                          90
                  ....*....|
gi 193203119   83 YINTGMFDGI 92
Cdd:pfam00106 181 GVDTDMTKEL 190

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119  16 TKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYalKKDVKTTVVCPIYINTGM------- 88
Cdd:cd05332  120 TKAALPHLIERSQGSIVVVSSIAGKIGVPFRTAYAASKHALQGFFDSLRAELS--EPNISVTVVCPGLIDTNIamnalsg 197

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 193203119  89 -FDGIATKWPTLLPILSPEYVVDCIMEAVLTDRAFLAIPKF 128
Cdd:cd05332  198 dGSMSAKMDDTTANGMSPEECALEILKAIALRKREVFYARQ 238

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 193203119   7 VNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELyaLKKDVKTTVVCPIYINT 86
Cdd:cd05333  107 VNLTGVFNVTQAVIRAMIKRRSGRIINISSVVGLIGNPGQANYAASKAGVIGFTKSLAKEL--ASRGITVNAVAPGFIDT 184

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 193203119  87 GMFDGIatkwptllpilsPEYVVDCIMEAVLTDR-----------AFLAIPKFSYI 131
Cdd:cd05333  185 DMTDAL------------PEKVKEKILKQIPLGRlgtpeevanavAFLASDDASYI 228

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   3 KTVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELyAlKKDVKTTVVCPI 82
Cdd:PRK05653 108 RVIDVNLTGTFNVVRAALPPMIKARYGRIVNISSVSGVTGNPGQTNYSAAKAGVIGFTKALALEL-A-SRGITVNAVAPG 185

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 193203119  83 YINTGMFDGI-------ATKWPTLLPILSPEYVVDCImeavltdrAFLAIPKFSYI 131
Cdd:PRK05653 186 FIDTDMTEGLpeevkaeILKEIPLGRLGQPEEVANAV--------AFLASDAASYI 233

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. 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 193203119   3 KTVSVNTNALFFTTKNFLPGMLESNKGH---IVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYaLKKDVKTTVV 79
Cdd:cd05323  105 KTIDVNLTGVINTTYLALHYMDKNKGGKggvIVNIGSVAGLYPAPQFPVYSASKHGVVGFTRSLADLLE-YKTGVRVNAI 183

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 193203119  80 CPIYINTGMFDGIATKWPTLL---PILSPEYVVDCIMEAV 116
Cdd:cd05323  184 CPGFTNTPLLPDLVAKEAEMLpsaPTQSPEVVAKAIVYLI 223

Polyketide ketoreductase, classical (c) SDR; Polyketide ketoreductase (KR) is a classical SDR with a characteristic NAD-binding pattern and active site tetrad. Aromatic polyketides include various aromatic compounds of pharmaceutical interest. Polyketide KR, part of the type II polyketide synthase (PKS) complex, is comprised of stand-alone domains that resemble the domains found in fatty acid synthase and multidomain type I PKS. 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 193203119   5 VSVNTNALFFTTKNFLP--GMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELyaLKKDVKTTVVCPI 82
Cdd:cd08945  108 VETNLTGVFRVTKEVLKagGMLERGTGRIINIASTGGKQGVVHAAPYSASKHGVVGFTKALGLEL--ARTGITVNAVCPG 185

                 ....*.
gi 193203119  83 YINTGM 88
Cdd:cd08945  186 FVETPM 191

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   5 VSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASElYAlKKDVKTTVVCPIYI 84
Cdd:PRK06172 113 MGVNVKGVWLCMKYQIPLMLAQGGGAIVNTASVAGLGAAPKMSIYAASKHAVIGLTKSAAIE-YA-KKGIRVNAVCPAVI 190

                 ....*
gi 193203119  85 NTGMF 89
Cdd:PRK06172 191 DTDMF 195

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 193203119  16 TKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYALkkDVKTTVVCPIYINTGMFDGIATK 95
Cdd:cd05374  113 TRAFLPLMRKQGSGRIVNVSSVAGLVPTPFLGPYCASKAALEALSESLRLELAPF--GIKVTIIEPGPVRTGFADNAAGS 190

                 ..
gi 193203119  96 WP 97
Cdd:cd05374  191 AL 192

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   6 SVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASElYAlKKDVKTTVVCPIYIN 85
Cdd:PRK06550  97 DTNLTSTFLLTRAYLPQMLERKSGIIINMCSIASFVAGGGGAAYTASKHALAGFTKQLALD-YA-KDGIQVFGIAPGAVK 174

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 193203119  86 TGM----F-DGIATKW-PTLLPI---LSPEYVVDcimeavLTDraFLAIPKFSYI 131
Cdd:PRK06550 175 TPMtaadFePGGLADWvARETPIkrwAEPEEVAE------LTL--FLASGKADYM 221

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   7 VNTNalFFTTKNF----LPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELyaLKKDVKTTVVCPI 82
Cdd:cd08939  110 MDVN--YFGSLNVahavLPLMKEQRPGHIVFVSSQAALVGIYGYSAYCPSKFALRGLAESLRQEL--KPYNIRVSVVYPP 185

                 ....*...
gi 193203119  83 YINTGMFD 90
Cdd:cd08939  186 DTDTPGFE 193

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   3 KTVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASElYAlKKDVKTTVVCPI 82
Cdd:PRK05565 109 RVIDVNLTGVMLLTRYALPYMIKRKSGVIVNISSIWGLIGASCEVLYSASKGAVNAFTKALAKE-LA-PSGIRVNAVAPG 186

                 ....*.
gi 193203119  83 YINTGM 88
Cdd:PRK05565 187 AIDTEM 192

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 193203119   7 VNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYALkkDVKTTVVCP 81
Cdd:PRK06180 108 VNVFGAVAMTKAVLPGMRARRRGHIVNITSMGGLITMPGIGYYCGSKFALEGISESLAKEVAPF--GIHVTAVEP 180

SDR family oxidoreductase UcpA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   5 VSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGK-CGVAGLVDYCASKHGAVGFNDSLASElYAlKKDVKTTVVCPIY 83
Cdd:PRK08226 110 IDINIKGVWNVTKAVLPEMIARKDGRIVMMSSVTGDmVADPGETAYALTKAAIVGLTKSLAVE-YA-QSGIRVNAICPGY 187

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119  84 INTGMFDGIATKW-PTllpilSPEYVVDCIMEAVLTDR-----------AFLAIPKFSYI 131
Cdd:PRK08226 188 VRTPMAESIARQSnPE-----DPESVLTEMAKAIPLRRladplevgelaAFLASDESSYL 242

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   5 VSVNTNALFFTTKNFLPGMLESNK-GHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYALKKDVKTtvVCPIY 83
Cdd:PRK12827 115 IDVNLDGFFNVTQAALPPMIRARRgGRIVNIASVAGVRGNRGQVNYAASKAGLIGLTKTLANELAPRGITVNA--VAPGA 192

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 193203119  84 INTGMFDGIATKWPTLLPI-----LSPEYVVDCImeavltdrAFLAIPKFSYI 131
Cdd:PRK12827 193 INTPMADNAAPTEHLLNPVpvqrlGEPDEVAALV--------AFLVSDAASYV 237

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119  20 LPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYALKKDVKTTVVCPIYINTGMFDGIATKWPTL 99
Cdd:cd05360  120 LPHLRRRGGGALINVGSLLGYRSAPLQAAYSASKHAVRGFTESLRAELAHDGAPISVTLVQPTAMNTPFFGHARSYMGKK 199

                         90       100
                 ....*....|....*....|
gi 193203119 100 L----PILSPEYVVDCIMEA 115
Cdd:cd05360  200 PkpppPIYQPERVAEAIVRA 219

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   3 KTVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYALKkdVKTTVVCPI 82
Cdd:PRK07231 108 RIFAVNVKSPYLWTQAAVPAMRGEGGGAIVNVASTAGLRPRPGLGWYNASKGAVITLTKALAAELGPDK--IRVNAVAPV 185

                 ....*.
gi 193203119  83 YINTGM 88
Cdd:PRK07231 186 VVETGL 191

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119  17 KNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYalKKDVKTTVVCPIYINTGMFDGIATKW 96
Cdd:PRK05650 117 KAFLPLFKRQKSGRIVNIASMAGLMQGPAMSSYNVAKAGVVALSETLLVELA--DDEIGVHVVCPSFFQTNLLDSFRGPN 194

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 193203119  97 PTL----------LPIlSPEYVVDCIMEAVlTDRAFLAIP 126
Cdd:PRK05650 195 PAMkaqvgkllekSPI-TAADIADYIYQQV-AKGEFLILP 232

3-hydroxybutyrate dehydrogenase; This model represents a subfamily of the short chain dehydrogenases. Characterized members so far as 3-hydroxybutyrate dehydrogenases and are found in species that accumulate ester polmers called polyhydroxyalkanoic acids (PHAs) under certain conditions. Several members of the family are from species not known to accumulate PHAs, including Oceanobacillus iheyensis and Bacillus subtilis. However, polymer formation is not required for there be a role for 3-hydroxybutyrate dehydrogenase; it may be members of this family have the same function in those species.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119    5 VSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYAlkKDVKTTVVCPIYI 84
Cdd:TIGR01963 106 IAVMLTSAFHTIRAALPHMKKQGWGRIINIASAHGLVASPFKSAYVAAKHGLIGLTKVLALEVAE--HGITVNAICPGYV 183

                  ..
gi 193203119   85 NT 86
Cdd:TIGR01963 184 RT 185

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 193203119   4 TVSVNTNALFFTTKNFLPGMLESNKGHIVTIASMAGKC-GVAGLVDYCASKHGAVGFNDSLASELyaLKKDVKTTVVCPI 82
Cdd:cd05368   97 AMNLNVRSMYLMIKAVLPKMLARKDGSIINMSSVASSIkGVPNRFVYSTTKAAVIGLTKSVAADF--AQQGIRCNAICPG 174

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 193203119  83 YINTGMFDGIATKWPtllpilSPEYVVDCIMEAVLTDR 120
Cdd:cd05368  175 TVDTPSLEERIQAQP------DPEEALKAFAARQPLGR 206

classical (c) SDR, subgroup 6; These proteins are members of the classical SDR family, with a canonical active site tetrad and a fairly well conserved typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119  20 LPGMLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELyaLKKDVKTTVVCPIYINTGMFDGIAtkwpTL 99
Cdd:cd05350  118 LPQFRAKGRGHLVLISSVAALRGLPGAAAYSASKAALSSLAESLRYDV--KKRGIRVTVINPGFIDTPLTANMF----TM 191

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 193203119 100 LPILSPEYVVDCIMEAVLTDRAFLAIPKFSYIFIALAGLLPT 141
Cdd:cd05350  192 PFLMSVEQAAKRIYKAIKKGAAEPTFPWRLAVPLRLLKLLPE 233

SDR family oxidoreductase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 193203119   4 TVSVNTNALFFTTKNFLPGmLESNKGHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASELYalKKDVKTTVVCP 81
Cdd:PRK07326 109 VIDTNLTGAFYTIKAAVPA-LKRGGGYIINISSLAGTNFFAGGAAYNASKFGLVGFSEAAMLDLR--QYGIKVSTIMP 183

3-hydroxybutyrate dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203119   3 KTVSVNTNALFFTTKNFLPGMLESNK-GHIVTIASMAGKCGVAGLVDYCASKHGAVGFNDSLASElyALKKDVKTTVVCP 81
Cdd:PRK13394 110 KMQAIHVDGAFLTTKAALKHMYKDDRgGVVIYMGSVHSHEASPLKSAYVTAKHGLLGLARVLAKE--GAKHNVRSHVVCP 187

                 ....*....
gi 193203119  82 IYINTGMFD 90
Cdd:PRK13394 188 GFVRTPLVD 196