Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAFS 82
Cdd:COG0300    86 LVNNAGVGGGGPFEELDLEDLRRVFEVNVFGPVRLTRALLPlMRARGRGRIVNVSSVAGLRGLPGMAAYAASKAALEGFS 165

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034634989  83 DCLRYEMYPLGVKVSVVEPG----NFIAAT------SLYSPEsiqAIAKKMWE 125
Cdd:COG0300   166 ESLRAELAPTGVRVTAVCPGpvdtPFTARAgapagrPLLSPE---EVARAILR 215

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   2 WGLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEA 80
Cdd:pfam00106  79 DILVNNAGITGLGPFSELSDEDWERVIDVNLTGVFNLTRAVLPaMIKGSGGRIVNISSVAGLVPYPGGSAYSASKAAVIG 158

                          90       100
                  ....*....|....*....|....
gi 1034634989  81 FSDCLRYEMYPLGVKVSVVEPGNF 104
Cdd:pfam00106 159 FTRSLALELAPHGIRVNAVAPGGV 182

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 1034634989   1 MWGLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIRRAK-GRVVNISSMLGRMANPARSPYCITKFGVE 79
Cdd:cd05374    75 IDVLVNNAGYGLFGPLEETSIEEVRELFEVNVFGPLRVTRAFLPLMRKQGsGRIVNVSSVAGLVPTPFLGPYCASKAALE 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989  80 AFSDCLRYEMYPLGVKVSVVEPGNFIAATSLYSPESIQAIakkmweelpevvrkDYGKKYFDEKIAKMETYCSSGSTDTS 159
Cdd:cd05374   155 ALSESLRLELAPFGIKVTIIEPGPVRTGFADNAAGSALED--------------PEISPYAPERKEIKENAAGVGSNPGD 220

                         170       180
                  ....*....|....*....|....*...
gi 1034634989 160 P--VIDAVTHALTATTPYTRYHPMDYYW 185
Cdd:cd05374   221 PekVADVIVKALTSESPPLRYFLGSDAL 248

short chain dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIRRAK-GRVVNISSMLGRMANPARSPYCITKFGVEAFS 82
Cdd:PRK06182   78 LVNNAGYGSYGAIEDVPIDEARRQFEVNLFGAARLTQLVLPHMRAQRsGRIINISSMGGKIYTPLGAWYHATKFALEGFS 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989  83 DCLRYEMYPLGVKVSVVEPG------NFIAATSL--------YSPESiQAIAKKMweelpevvRKDYGkkyfdekiakme 148
Cdd:PRK06182  158 DALRLEVAPFGIDVVVIEPGgiktewGDIAADHLlktsgngaYAEQA-QAVAASM--------RSTYG------------ 216

                         170       180       190
                  ....*....|....*....|....*....|.
gi 1034634989 149 tycSSGSTDTSPVIDAVTHALTATTPYTRYH 179
Cdd:PRK06182  217 ---SGRLSDPSVIADAISKAVTARRPKTRYA 244

classical (c) 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 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 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 1034634989   3 GLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAF 81
Cdd:cd05233    77 ILVNNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPhMKKQGGGRIVNISSVAGLRPLPGQAAYAASKAALEGL 156

                          90       100
                  ....*....|....*....|.
gi 1034634989  82 SDCLRYEMYPLGVKVSVVEPG 102
Cdd:cd05233   157 TRSLALELAPYGIRVNAVAPG 177

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 1034634989   3 GLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAF 81
Cdd:cd05332    84 ILINNAGISMRSLFHDTSIDVDRKIMEVNYFGPVALTKAALPhLIERSQGSIVVVSSIAGKIGVPFRTAYAASKHALQGF 163

                          90       100
                  ....*....|....*....|.
gi 1034634989  82 SDCLRYEMYPLGVKVSVVEPG 102
Cdd:cd05332   164 FDSLRAELSEPNISVTVVCPG 184

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIRRAK-GRVVNISSMLGRMANPARSPYCITKFGVEAFS 82
Cdd:PRK06914   85 LVNNAGYANGGFVEEIPVEEYRKQFETNVFGAISVTQAVLPYMRKQKsGKIINISSISGRVGFPGLSPYVSSKYALEGFS 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989  83 DCLRYEMYPLGVKVSVVEPGNFiaATSLYSpESIQAIAKKMWEELPevvrkdYgKKYFDekiaKMETYCSSGStDTSP-- 160
Cdd:PRK06914  165 ESLRLELKPFGIDVALIEPGSY--NTNIWE-VGKQLAENQSETTSP------Y-KEYMK----KIQKHINSGS-DTFGnp 229

                         170       180
                  ....*....|....*....|
gi 1034634989 161 --VIDAVTHALTATTPYTRY 178
Cdd:PRK06914  230 idVANLIVEIAESKRPKLRY 249

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   2 WG----LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIRRAK-GRVVNISSMLGRMANPARSPYCITKF 76
Cdd:PRK05650   75 WGgidvIVNNAGVASGGFFEELSLEDWDWQIAINLMGVVKGCKAFLPLFKRQKsGRIVNIASMAGLMQGPAMSSYNVAKA 154

                          90       100
                  ....*....|....*....|....*...
gi 1034634989  77 GVEAFSDCLRYEMYPLGVKVSVVEPGNF 104
Cdd:PRK05650  155 GVVALSETLLVELADDEIGVHVVCPSFF 182

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 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIR-RAKGRVVNISSMLGRMANPARSPYCITKFGVEAFS 82
Cdd:cd08939    86 VVNCAGISIPGLFEDLTAEEFERGMDVNYFGSLNVAHAVLPLMKeQRPGHIVFVSSQAALVGIYGYSAYCPSKFALRGLA 165

                          90       100
                  ....*....|....*....|..
gi 1034634989  83 DCLRYEMYPLGVKVSVVEPGNF 104
Cdd:cd08939   166 ESLRQELKPYNIRVSVVYPPDT 187

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 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIR-RAKGRVVNISSMLGRMANPARSPYCITKFGVEAFS 82
Cdd:cd08934    84 LVNNAGIMLLGPVEDADTTDWTRMIDTNLLGLMYTTHAALPHHLlRNKGTIVNISSVAGRVAVRNSAVYNATKFGVNAFS 163

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034634989  83 DCLRYEMYPLGVKVSVVEPGnfIAATSLYSPESiQAIAKKMWEELPEVVRK 133
Cdd:cd08934   164 EGLRQEVTERGVRVVVIEPG--TVDTELRDHIT-HTITKEAYEERISTIRK 211

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGR-VVNISSMLGRMANPARSPYCITKFGVEAF 81
Cdd:PRK07832   82 VMNIAGISAWGTVDRLTHEQWRRMVDVNLMGPIHVIETFVPpMVAAGRGGhLVNVSSAAGLVALPWHAAYSASKFGLRGL 161

                          90       100
                  ....*....|....*....|.
gi 1034634989  82 SDCLRYEMYPLGVKVSVVEPG 102
Cdd:PRK07832  162 SEVLRFDLARHGIGVSVVVPG 182

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   1 MWGLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIR-RAKGRVVNISSMLGRMANPARSPYCITKFGVE 79
Cdd:PRK08017   75 LYGLFNNAGFGVYGPLSTISRQQMEQQFSTNFFGTHQLTMLLLPAMLpHGEGRIVMTSSVMGLISTPGRGAYAASKYALE 154

                          90       100
                  ....*....|....*....|...
gi 1034634989  80 AFSDCLRYEMYPLGVKVSVVEPG 102
Cdd:PRK08017  155 AWSDALRMELRHSGIKVSLIEPG 177

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 1034634989   5 VNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAFSD 83
Cdd:cd05360    82 VNNAGVAVFGRFEDVTPEEFRRVFDVNYLGHVYGTLAALPhLRRRGGGALINVGSLLGYRSAPLQAAYSASKHAVRGFTE 161

                          90
                  ....*....|....*.
gi 1034634989  84 CLRYEMYPLGVKVSVV 99
Cdd:cd05360   162 SLRAELAHDGAPISVT 177

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   3 GLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAF 81
Cdd:PRK05557   86 ILVNNAGITRDNLLMRMKEEDWDRVIDTNLTGVFNLTKAVARpMMKQRSGRIINISSVVGLMGNPGQANYAASKAGVIGF 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1034634989  82 SDCLRYEMYPLGVKVSVVEPGnFIA--ATSLYSPESIQAIAKKM 123
Cdd:PRK05557  166 TKSLARELASRGITVNAVAPG-FIEtdMTDALPEDVKEAILAQI 208

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   4 LVNNAGISTFGEVE-FTSLETYKQVaEVNLWGTVRMTKSFLPLIRR-AKGRVVNISSMLGRMANPARSPYCITKFGVEAF 81
Cdd:PRK08263   81 VVNNAGYGLFGMIEeVTESEARAQI-DTNFFGALWVTQAVLPYLREqRSGHIIQISSIGGISAFPMSGIYHASKWALEGM 159

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1034634989  82 SDCLRYEMYPLGVKVSVVEPGNFiaATSLYSP 113
Cdd:PRK08263  160 SEALAQEVAEFGIKVTLVEPGGY--STDWAGT 189

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAFS 82
Cdd:PRK07666   88 LINNAGISKFGKFLELDPAEWEKIIQVNLMGVYYATRAVLPsMIERQSGDIINISSTAGQKGAAVTSAYSASKFGVLGLT 167

                          90
                  ....*....|....*....
gi 1034634989  83 DCLRYEMYPLGVKVSVVEP 101
Cdd:PRK07666  168 ESLMQEVRKHNIRVTALTP 186

Porcine testicular carbonyl reductase (PTCR)-like, classical (c) SDRs; PTCR is a classical SDR which catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. Unlike most SDRs, PTCR functions as a monomer. This subgroup also includes human carbonyl reductase 1 (CBR1) and CBR3. CBR1 is an NADPH-dependent SDR with broad substrate specificity and may be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds. In addition it includes poppy NADPH-dependent salutaridine reductase which catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine, and Arabidopsis SDR1,a menthone reductase, which catalyzes the reduction of menthone to neomenthol, a compound with antimicrobial activity; SDR1 can also carry out neomenthol oxidation. 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 1034634989   4 LVNNAGISTFG-EVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIRRAK-GRVVNISSMLGRMAnparSPYCITKFGVEAF 81
Cdd:cd05324    82 LVNNAGIAFKGfDDSTPTREQARETMKTNFFGTVDVTQALLPLLKKSPaGRIVNVSSGLGSLT----SAYGVSKAALNAL 157

                          90       100
                  ....*....|....*....|.
gi 1034634989  82 SDCLRYEMYPLGVKVSVVEPG 102
Cdd:cd05324   158 TRILAKELKETGIKVNACCPG 178

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAFS 82
Cdd:PRK09291   77 LLNNAGIGEAGAVVDIPVELVRELFETNVFGPLELTQGFVRkMVARGKGKVVFTSSMAGLITGPFTGAYCASKHALEAIA 156

                          90       100
                  ....*....|....*....|..
gi 1034634989  83 DCLRYEMYPLGVKVSVVEPGNF 104
Cdd:PRK09291  157 EAMHAELKPFGIQVATVNPGPY 178

HetN oxidoreductase-like, classical (c) SDR; This subgroup includes Anabaena sp. strain PCC 7120 HetN, a putative oxidoreductase involved in heterocyst differentiation, and related proteins. 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 1034634989   3 GLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAF 81
Cdd:cd08932    76 VLVHNAGIGRPTTLREGSDAELEAHFSINVIAPAELTRALLPaLREAGSGRVVFLNSLSGKRVLAGNAGYSASKFALRAL 155

                          90       100
                  ....*....|....*....|.
gi 1034634989  82 SDCLRYEMYPLGVKVSVVEPG 102
Cdd:cd08932   156 AHALRQEGWDHGVRVSAVCPG 176

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034634989   2 WG----LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIRRAKGRVVNISSMLGRMANPARSPYCITKFG 77
Cdd:PRK07326   80 FGgldvLIANAGVGHFAPVEELTPEEWRLVIDTNLTGAFYTIKAAVPALKRGGGYIINISSLAGTNFFAGGAAYNASKFG 159

                          90       100
                  ....*....|....*....|....*
gi 1034634989  78 VEAFSDCLRYEMYPLGVKVSVVEPG 102
Cdd:PRK07326  160 LVGFSEAAMLDLRQYGIKVSTIMPG 184

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 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAFS 82
Cdd:cd05339    80 LINNAGVVSGKKLLELPDEEIEKTFEVNTLAHFWTTKAFLPdMLERNHGHIVTIASVAGLISPAGLADYCASKAAAVGFH 159

                          90       100
                  ....*....|....*....|...
gi 1034634989  83 DCLRYEM---YPLGVKVSVVEPG 102
Cdd:cd05339   160 ESLRLELkayGKPGIKTTLVCPY 182

classical (c) SDR, subgroup 11; 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 1034634989   4 LVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLPLIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAFSD 83
Cdd:cd05364    87 LVNNAGILAKGGGEDQDIEEYDKVMNLNLRAVIYLTKLAVPHLIKTKGEIVNVSSVAGGRSFPGVLYYCISKAALDQFTR 166

                          90       100
                  ....*....|....*....|....*....
gi 1034634989  84 CLRYEMYPLGVKVSVVEPGnfIAATSLYS 112
Cdd:cd05364   167 CTALELAPKGVRVNSVSPG--VIVTGFHR 193

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 1034634989   3 GLVNNAGISTFGEVEFTSLETYKQVAEVNLWGTVRMTKSFLP-LIRRAKGRVVNISSMLGRMANPARSPYCITKFGVEAF 81
Cdd:cd05333    80 ILVNNAGITRDNLLMRMSEEDWDAVINVNLTGVFNVTQAVIRaMIKRRSGRIINISSVVGLIGNPGQANYAASKAGVIGF 159

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034634989  82 SDCLRYEMYPLGVKVSVVEPGnFIAAtslyspesiqaiakKMWEELPEVVRK 133
Cdd:cd05333   160 TKSLAKELASRGITVNAVAPG-FIDT--------------DMTDALPEKVKE 196