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 1381989231  32 AHFTLIDINEQALQQ--RVQALGNRASYALWDLFKPE---QLAEQWqkIRQNKPVDLLVNCAGIM---DIISFQGTGWQl 103
Cdd:cd05233    23 AKVVLADRNEEALAElaAIEALGGNAVAVQADVSDEEdveALVEEA--LEEFGRLDILVNNAGIArpgPLEELTDEDWD- 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 104 gwKLLSVNLISPLRLMDLALADMPAGGG--IINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPG 181
Cdd:cd05233   100 --RVLDVNLTGVFLLTRAALPHMKKQGGgrIVNISSVAGLRPLPGQAAYAASKAALEGLTRSLALELAPYGIRVNAVAPG 177

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1381989231 182 PIFSGLEAHARGQVKQGMVSKLIP---TGQAQDIAQEIV 217
Cdd:cd05233   178 LVDTPMLAKLGPEEAEKELAAAIPlgrLGTPEEVAEAVV 216

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  32 AHFTLIDINEQALQQRVQALGN---RASYALWDLFKPEQLAEQWQKIRQN-KPVDLLVNCAGIM---DIISFQGTGWQlg 104
Cdd:pfam00106  25 AKVVLVDRSEEKLEAVAKELGAlggKALFIQGDVTDRAQVKALVEQAVERlGRLDILVNNAGITglgPFSELSDEDWE-- 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 105 wKLLSVNLISPLRLMDLALADMPAGGG--IINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGP 182
Cdd:pfam00106 103 -RVIDVNLTGVFNLTRAVLPAMIKGSGgrIVNISSVAGLVPYPGGSAYSASKAAVIGFTRSLALELAPHGIRVNAVAPGG 181

                  .
gi 1381989231 183 I 183
Cdd:pfam00106 182 V 182

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 1381989231  32 AHFTLIDINEQALQQ--RVQALGNRASYALWDLFKPE---QLAEQWqkIRQNKPVDLLVNCAGIM---DIISFQGTGWQl 103
Cdd:cd05233    23 AKVVLADRNEEALAElaAIEALGGNAVAVQADVSDEEdveALVEEA--LEEFGRLDILVNNAGIArpgPLEELTDEDWD- 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 104 gwKLLSVNLISPLRLMDLALADMPAGGG--IINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPG 181
Cdd:cd05233   100 --RVLDVNLTGVFLLTRAALPHMKKQGGgrIVNISSVAGLRPLPGQAAYAASKAALEGLTRSLALELAPYGIRVNAVAPG 177

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1381989231 182 PIFSGLEAHARGQVKQGMVSKLIP---TGQAQDIAQEIV 217
Cdd:cd05233   178 LVDTPMLAKLGPEEAEKELAAAIPlgrLGTPEEVAEAVV 216

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 1381989231  32 AHFTLIDINEQALQ---QRVQALGNRASYALWDLFKPEQLAEQWQKIRQN-KPVDLLVNCAGIMDIISFQGT---GWQlg 104
Cdd:COG1028    31 ARVVITDRDAEALEaaaAELRAAGGRALAVAADVTDEAAVEALVAAAVAAfGRLDILVNNAGITPPGPLEELteeDWD-- 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 105 wKLLSVNLISPLRLMDLALADMPAGGG--IINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGP 182
Cdd:COG1028   109 -RVLDVNLKGPFLLTRAALPHMRERGGgrIVNISSIAGLRGSPGQAAYAASKAAVVGLTRSLALELAPRGIRVNAVAPGP 187

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1381989231 183 IFSGLEAHARG--QVKQGMVSKlIPT---GQAQDIA 213
Cdd:COG1028   188 IDTPMTRALLGaeEVREALAAR-IPLgrlGTPEEVA 222

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  32 AHFTLIDINEQALQQRVQALGN---RASYALWDLFKPEQLAEQWQKIRQN-KPVDLLVNCAGIM---DIISFQGTGWQlg 104
Cdd:pfam00106  25 AKVVLVDRSEEKLEAVAKELGAlggKALFIQGDVTDRAQVKALVEQAVERlGRLDILVNNAGITglgPFSELSDEDWE-- 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 105 wKLLSVNLISPLRLMDLALADMPAGGG--IINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGP 182
Cdd:pfam00106 103 -RVIDVNLTGVFNLTRAVLPAMIKGSGgrIVNISSVAGLVPYPGGSAYSASKAAVIGFTRSLALELAPHGIRVNAVAPGG 181

                  .
gi 1381989231 183 I 183
Cdd:pfam00106 182 V 182

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 1381989231  25 LAQRYPQahFTLIDINEQ---ALQQRVQALGNRASYALWDLFKPEQLAEQWQKIRQ-NKPVDLLVNCAGIMDIISFQGTG 100
Cdd:cd05339    19 FAKRGAK--VVILDINEKgaeETANNVRKAGGKVHYYKCDVSKREEVYEAAKKIKKeVGDVTILINNAGVVSGKKLLELP 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 101 WQLGWKLLSVNLISPLRLMDLALADMPAG--GGIINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKE---RNIHV 175
Cdd:cd05339    97 DEEIEKTFEVNTLAHFWTTKAFLPDMLERnhGHIVTIASVAGLISPAGLADYCASKAAAVGFHESLRLELKAygkPGIKT 176

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1381989231 176 LTVYPGPIFSGLeahargqvKQGMVSK---LIPTGQAQDIAQEIVDSFQRKKVRVIYPKAYAVAHYF 239
Cdd:cd05339   177 TLVCPYFINTGM--------FQGVKTPrplLAPILEPEYVAEKIVRAILTNQQMLYLPFYAYFLPIL 235

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 1381989231  23 QILAQRypQAHFTLIDINE-----QALQQrvQALGNRASYALWDLFKPEQLAEQWQKIRQN-KPVDLLVNCAGIMD-IIS 95
Cdd:cd05323    18 KLLLKK--GAKVAILDRNEnpgaaAELQA--INPKVKATFVQCDVTSWEQLAAAFKKAIEKfGRVDILINNAGILDeKSY 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  96 FQGTGWQLGW-KLLSVNLISPLRLMDLALADM-----PAGGGIINIASMAGRVPITGCAYYSGAKAGI-----AMASEIA 164
Cdd:cd05323    94 LFAGKLPPPWeKTIDVNLTGVINTTYLALHYMdknkgGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVvgftrSLADLLE 173

                         170       180
                  ....*....|....*....|....*....
gi 1381989231 165 HNElkerNIHVLTVYPG----PIFSGLEA 189
Cdd:cd05323   174 YKT----GVRVNAICPGftntPLLPDLVA 198

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 1381989231  61 DLFKPEQLAEQWQKIR-QNKPVDLLVNCAGIMDIISFQGTGWQLGWKLLSVNLISPLRLMDLAL-ADMPAGGG-IINIAS 137
Cdd:cd08932    53 DARDPEDARALVDALRdRFGRIDVLVHNAGIGRPTTLREGSDAELEAHFSINVIAPAELTRALLpALREAGSGrVVFLNS 132

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1381989231 138 MAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGPI 183
Cdd:cd08932   133 LSGKRVLAGNAGYSASKFALRALAHALRQEGWDHGVRVSAVCPGFV 178

3-oxoacyl-ACP reductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  49 QALGNRASYALWDLFKPEQLAEQWQKIRQNK-PVDLLVNCAGIMDIISFQGTGWQLGWKLLSVNLISPLRLMDLALADM- 126
Cdd:PRK12824   48 GFTEDQVRLKELDVTDTEECAEALAEIEEEEgPVDILVNNAGITRDSVFKRMSHQEWNDVINTNLNSVFNVTQPLFAAMc 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 127 -PAGGGIINIASMAGRVPITGCAYYSGAKAGI-----AMASEIAhnelkERNIHVLTVYPGPIFSGLEAHARGQVKQGMV 200
Cdd:PRK12824  128 eQGYGRIINISSVNGLKGQFGQTNYSAAKAGMigftkALASEGA-----RYGITVNCIAPGYIATPMVEQMGPEVLQSIV 202

                         170
                  ....*....|....*....
gi 1381989231 201 SKlIPT---GQAQDIAQEI 216
Cdd:PRK12824  203 NQ-IPMkrlGTPEEIAAAV 220

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 1381989231  42 QALQQRVQALGNRASYALWDLFKPEQLAEQWQK-IRQNKPVDLLVNCAGIM---DIISFQGTGWQlgwKLLSVNLISPLR 117
Cdd:cd08934    41 EALADELEAEGGKALVLELDVTDEQQVDAAVERtVEALGRLDILVNNAGIMllgPVEDADTTDWT---RMIDTNLLGLMY 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 118 LMDLALADMPA--GGGIINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGPIFSGLEAH----A 191
Cdd:cd08934   118 TTHAALPHHLLrnKGTIVNISSVAGRVAVRNSAVYNATKFGVNAFSEGLRQEVTERGVRVVVIEPGTVDTELRDHithtI 197

                         170       180
                  ....*....|....*....|....*.
gi 1381989231 192 RGQVKQGMVSKLIPTgQAQDIAQEIV 217
Cdd:cd08934   198 TKEAYEERISTIRKL-QAEDIAAAVR 222

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 1381989231  61 DLFKPEQLAEQ-WQKIRQNKPVDLLVNCAGIMDIISFQGTGWQLGWKLLSVNLISPLRLMDLALADM-PAGGG-IINIAS 137
Cdd:cd05374    54 DVTDEESIKAAvKEVIERFGRIDVLVNNAGYGLFGPLEETSIEEVRELFEVNVFGPLRVTRAFLPLMrKQGSGrIVNVSS 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 138 MAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGPIFSGLEAHA----------------RGQVKQGMVS 201
Cdd:cd05374   134 VAGLVPTPFLGPYCASKAALEALSESLRLELAPFGIKVTIIEPGPVRTGFADNAagsaledpeispyapeRKEIKENAAG 213

                         170
                  ....*....|....*..
gi 1381989231 202 KLIPTGQAQDIAQEIVD 218
Cdd:cd05374   214 VGSNPGDPEKVADVIVK 230

tetrahydroxynaphthalene/trihydroxynaphthalene reductase-like, classical (c) SDRs; 1,3,6,8-tetrahydroxynaphthalene reductase (4HNR) of Magnaporthe grisea and the related 1,3,8-trihydroxynaphthalene reductase (3HNR) are typical members of the SDR family containing the canonical glycine rich NAD(P)-binding site and active site tetrad, and function in fungal melanin biosynthesis. This subgroup also includes an SDR from Norway spruce that may function to protect against both biotic and abitoic stress. 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 1381989231  43 ALQQRVQALGNRASYALWDLFKPEQLAEQWQKIRQN-KPVDLLVNCAGIMDIISFQGTGWQLGWKLLSVNLISPLRLMDL 121
Cdd:cd05362    43 EVVAEIEAAGGKAIAVQADVSDPSQVARLFDAAEKAfGGVDILVNNAGVMLKKPIAETSEEEFDRMFTVNTKGAFFVLQE 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 122 ALADMPAGGGIINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGPI----FSGLEAHA--RGQV 195
Cdd:cd05362   123 AAKRLRDGGRIINISSSLTAAYTPNYGAYAGSKAAVEAFTRVLAKELGGRGITVNAVAPGPVdtdmFYAGKTEEavEGYA 202

                         170
                  ....*....|....*...
gi 1381989231 196 KQGMVSKLiptGQAQDIA 213
Cdd:cd05362   203 KMSPLGRL---GEPEDIA 217

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  36 LIDINEQAL---QQRVQALGNRASYALWDLFKPEQLAEQWQKI-RQNKPVDLLVNCAGIM---DIISFQGTGWQlgwKLL 108
Cdd:cd05347    34 INSRNEEKAeeaQQLIEKEGVEATAFTCDVSDEEAIKAAVEAIeEDFGKIDILVNNAGIIrrhPAEEFPEAEWR---DVI 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 109 SVNLISPLRLMDLALADM-PAGGG-IINIASM---AGRVPITGcayYSGAKAGIAMASEIAHNELKERNIHVLTVYPGPI 183
Cdd:cd05347   111 DVNLNGVFFVSQAVARHMiKQGHGkIINICSLlseLGGPPVPA---YAASKGGVAGLTKALATEWARHGIQVNAIAPGYF 187

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1381989231 184 FSGLEAHARG-QVKQGMVSKLIP---TGQAQDI 212
Cdd:cd05347   188 ATEMTEAVVAdPEFNDDILKRIPagrWGQPEDL 220

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  40 NEQALQQRVQALGNRASYALwDLFKPEQLAEQWQKIRQNKP-VDLLVNCAGIMDIISFQGTGWQLGwKL---LSVNLISP 115
Cdd:cd05370    38 REERLAEAKKELPNIHTIVL-DVGDAESVEALAEALLSEYPnLDILINNAGIQRPIDLRDPASDLD-KAdteIDTNLIGP 115

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 116 LRLmdlALADMP-----AGGGIINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGPIFSGLeaH 190
Cdd:cd05370   116 IRL---IKAFLPhlkkqPEATIVNVSSGLAFVPMAANPVYCATKAALHSYTLALRHQLKDTGVEVVEIVPPAVDTEL--H 190

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1381989231 191 ARGQVKQGMVSKLIPTgqaQDIAQEIVDSFQRKKVRV 227
Cdd:cd05370   191 EERRNPDGGTPRKMPL---DEFVDEVVAGLERGREEI 224

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  38 DINEQALQ---QRVQALGNRASYALWDLFKPEQLAEQWQK-IRQNKPVDLLVNCAGIMDiisfQGTGWQLG---WK-LLS 109
Cdd:PRK12826   37 DICGDDAAataELVEAAGGKARARQVDVRDRAALKAAVAAgVEDFGRLDILVANAGIFP----LTPFAEMDdeqWErVID 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231 110 VNLISPLRLMDLALADM-PAGGG-IINIASMAGR-VPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPGPIFS- 185
Cdd:PRK12826  113 VNLTGTFLLTQAALPALiRAGGGrIVLTSSVAGPrVGYPGLAHYAASKAGLVGFTRALALELAARNITVNSVHPGGVDTp 192

                         170       180       190
                  ....*....|....*....|....*....|.
gi 1381989231 186 GLEAHARGQVKQGMVSkLIPT---GQAQDIA 213
Cdd:PRK12826  193 MAGNLGDAQWAEAIAA-AIPLgrlGEPEDIA 222

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  31 QAHFTLIDINEQALQQRVQALGNRASYALWDLFKPEQLAEQW-QKIRQNKPVDLLVNCAGIMDIISFQGTGWQlgW-KLL 108
Cdd:PRK08265   30 GARVAIVDIDADNGAAVAASLGERARFIATDITDDAAIERAVaTVVARFGRVDILVNLACTYLDDGLASSRAD--WlAAL 107

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1381989231 109 SVNLISPLRLMDLALADMPAGGG-IINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELKERNIHVLTVYPG 181
Cdd:PRK08265  108 DVNLVSAAMLAQAAHPHLARGGGaIVNFTSISAKFAQTGRWLYPASKAAIRQLTRSMAMDLAPDGIRVNSVSPG 181

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  26 AQRYPQ--AHFTLIDINEQALQQRVQALGN--RASYALWDLFKPEQLAEQWQK-IRQNKPVDLLVNCAGI---------M 91
Cdd:PRK07231   22 ARRFAAegARVVVTDRNEEAAERVAAEILAggRAIAVAADVSDEADVEAAVAAaLERFGSVDILVNNAGTthrngplldV 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1381989231  92 DIISFQgtgwqlgwKLLSVNLISPLRLMDLAL-ADMPAGGG-IINIASMAGRVPITGCAYYSGAKAGIAMASEIAHNELK 169
Cdd:PRK07231  102 DEAEFD--------RIFAVNVKSPYLWTQAAVpAMRGEGGGaIVNVASTAGLRPRPGLGWYNASKGAVITLTKALAAELG 173

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1381989231 170 ERNIHVLTVYPGPIFSGLEAHARGQVKQGMVSKLIPT------GQAQDIA 213
Cdd:PRK07231  174 PDKIRVNAVAPVVVETGLLEAFMGEPTPENRAKFLATiplgrlGTPEDIA 223