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 2462538571   1 MAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDKILSVNVKSPALLLSQL 80
Cdd:cd08936    51 VATLQGEGLSVTGTVCHVGKAEDRERLVATAVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDKILDVNVKATALMTKAV 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  81 LPYMENRRG-AVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESLWKN 159
Cdd:cd08936   131 VPEMEKRGGgSVVIVSSVAAFHPFPGLGPYNVSKTALLGLTKNLAPELAPRNIRVNCLAPGLIKTSFSSALWMDKAVEES 210

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 2462538571 160 FKEHHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:cd08936   211 MKETLRIRRLGQPEDCAGIVSFLCSEDASYITGETVVVGG 250

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. 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 2462538571   1 MAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDKILSVNVKSPALLLSQL 80
Cdd:cd08936    51 VATLQGEGLSVTGTVCHVGKAEDRERLVATAVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDKILDVNVKATALMTKAV 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  81 LPYMENRRG-AVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESLWKN 159
Cdd:cd08936   131 VPEMEKRGGgSVVIVSSVAAFHPFPGLGPYNVSKTALLGLTKNLAPELAPRNIRVNCLAPGLIKTSFSSALWMDKAVEES 210

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 2462538571 160 FKEHHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:cd08936   211 MKETLRIRRLGQPEDCAGIVSFLCSEDASYITGETVVVGG 250

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571   7 EGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGV-NPLVGSTLGTSEQIWDKILSVNVKSPALLLSQLLPYMe 85
Cdd:pfam13561  41 EELGAAVLPCDVTDEEQVEALVAAAVEKFGRLDILVNNAGFaPKLKGPFLDTSREDFDRALDVNLYSLFLLAKAALPLM- 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  86 NRRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESLWKNFKEHHQ 165
Cdd:pfam13561 120 KEGGSIVNLSSIGAERVVPNYNAYGAAKAALEALTRYLAVELGPRGIRVNAISPGPIKTLAASGIPGFDELLAAAEARAP 199

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 2462538571 166 LQRIGESEDCAGIVSFLCSPDASYVNGENIAV-AGYS 201
Cdd:pfam13561 200 LGRLGTPEEVANAAAFLASDLASYITGQVLYVdGGYT 236

pteridine reductase; Pteridine reductase is an enzyme used by trypanosomatids (including Trypanosoma cruzi and Leishmania major) to obtain reduced pteridines by salvage rather than biosynthetic pathways. Enzymes in T. cruzi described as pteridine reductase 1 (PTR1) and pteridine reductase 2 (PTR2) have different activity profiles. PTR1 is more active with with fully oxidized biopterin and folate than with reduced forms, while PTR2 reduces dihydrobiopterin and dihydrofolate but not oxidized pteridines. T. cruzi PTR1 and PTR2 are more similar to each other in sequence than either is to the pteridine reductase of Leishmania major, and all are included in this family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571 102 PVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIiktDFSKVFHGNESLWKNFKEHHQLQRIGESEDCAGIVSF 181
Cdd:TIGR02685 166 PLLGFTMYTMAKHALEGLTRSAALELAPLQIRVNGVAPGL---SLLPDAMPFEVQEDYRRKVPLGQREASAEQIADVVIF 242

                          90
                  ....*....|....*...
gi 2462538571 182 LCSPDASYVNGENIAVAG 199
Cdd:TIGR02685 243 LVSPKAKYITGTCIKVDG 260

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. 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 2462538571   1 MAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDKILSVNVKSPALLLSQL 80
Cdd:cd08936    51 VATLQGEGLSVTGTVCHVGKAEDRERLVATAVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDKILDVNVKATALMTKAV 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  81 LPYMENRRG-AVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESLWKN 159
Cdd:cd08936   131 VPEMEKRGGgSVVIVSSVAAFHPFPGLGPYNVSKTALLGLTKNLAPELAPRNIRVNCLAPGLIKTSFSSALWMDKAVEES 210

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 2462538571 160 FKEHHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:cd08936   211 MKETLRIRRLGQPEDCAGIVSFLCSEDASYITGETVVVGG 250

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 2462538571   2 AKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVGSTLGTSEQiWDKILSVNVKSPALLLSQLL 81
Cdd:cd05233    39 AAIEALGGNAVAVQADVSDEEDVEALVEEALEEFGRLDILVNNAGIARPGPLEELTDED-WDRVLDVNLTGVFLLTRAAL 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  82 PYM-ENRRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFhGNESLWKNF 160
Cdd:cd05233   118 PHMkKQGGGRIVNISSVAGLRPLPGQAAYAASKAALEGLTRSLALELAPYGIRVNAVAPGLVDTPMLAKL-GPEEAEKEL 196

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 2462538571 161 KEHHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAV 197
Cdd:cd05233   197 AAAIPLGRLGTPEEVAEAVVFLASDEASYITGQVIPV 233

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571   6 GEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDKILSVNVKSPALLLSQLLPYM- 84
Cdd:PRK07231   50 LAGGRAIAVAADVSDEADVEAAVAAALERFGSVDILVNNAGTTHRNGPLLDVDEAEFDRIFAVNVKSPYLWTQAAVPAMr 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  85 ENRRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSkvfhgnESLWKNFKEHH 164
Cdd:PRK07231  130 GEGGGAIVNVASTAGLRPRPGLGWYNASKGAVITLTKALAAELGPDKIRVNAVAPVVVETGLL------EAFMGEPTPEN 203

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 2462538571 165 Q--------LQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:PRK07231  204 RakflatipLGRLGTPEDIANAALFLASDEASWITGVTLVVDG 246

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571   4 LQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPlVGSTLGTSEQIWDKILSVNVKSPALLLSQLLPY 83
Cdd:PRK05565   50 IKEEGGDAIAVKADVSSEEDVENLVEQIVEKFGKIDILVNNAGISN-FGLVTDMTDEEWDRVIDVNLTGVMLLTRYALPY 128

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  84 MENRRGAVIL-VSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESlwKNFKE 162
Cdd:PRK05565  129 MIKRKSGVIVnISSIWGLIGASCEVLYSASKGAVNAFTKALAKELAPSGIRVNAVAPGAIDTEMWSSFSEEDK--EGLAE 206

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 2462538571 163 HHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:PRK05565  207 EIPLGRLGKPEEIAKVVLFLASDDASYITGQIITVDG 243

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571   2 AKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGV---NPLVGstlgTSEQIWDKILSVNVKSPALLLS 78
Cdd:PRK12825   49 EAVEALGRRAQAVQADVTDKAALEAAVAAAVERFGRIDILVNNAGIfedKPLAD----MSDDEWDEVIDVNLSGVFHLLR 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  79 QLLPYMENRR-GAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFskvfhgnesLW 157
Cdd:PRK12825  125 AVVPPMRKQRgGRIVNISSVAGLPGWPGRSNYAAAKAGLVGLTKALARELAEYGITVNMVAPGDIDTDM---------KE 195

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 2462538571 158 KNFKEHHQ-------LQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:PRK12825  196 ATIEEAREakdaetpLGRSGTPEDIARAVAFLCSDASDYITGQVIEVTG 244

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 2462538571   2 AKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVnplvgsT-----LGTSEQIWDKILSVNVKSPALL 76
Cdd:cd05333    42 EEIKALGGNAAALEADVSDREAVEALVEKVEAEFGPVDILVNNAGI------TrdnllMRMSEEDWDAVINVNLTGVFNV 115

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  77 LSQLLPYM-ENRRGAVILVSSIAAY--NPVVAlgVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFhgN 153
Cdd:cd05333   116 TQAVIRAMiKRRSGRIINISSVVGLigNPGQA--NYAASKAGVIGFTKSLAKELASRGITVNAVAPGFIDTDMTDAL--P 191

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 2462538571 154 ESLWKNFKEHHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:cd05333   192 EKVKEKILKQIPLGRLGTPEEVANAVAFLASDDASYITGQVLHVNG 237

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 2462538571   2 AKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLvGSTLGTSEQIWDKILSVNVKSPALLLSQLL 81
Cdd:cd05362    46 AEIEAAGGKAIAVQADVSDPSQVARLFDAAEKAFGGVDILVNNAGVMLK-KPIAETSEEEFDRMFTVNTKGAFFVLQEAA 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  82 PYMeNRRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFskvFHGNES--LWKN 159
Cdd:cd05362   125 KRL-RDGGRIINISSSLTAAYTPNYGAYAGSKAAVEAFTRVLAKELGGRGITVNAVAPGPVDTDM---FYAGKTeeAVEG 200

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 2462538571 160 FKEHHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:cd05362   201 YAKMSPLGRLGEPEDIAPVVAFLASPDGRWVNGQVIRANG 240

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571   2 AKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLvGSTLGTSEQIWDKILSVNVKSPALLLSQLL 81
Cdd:COG0300    47 AELRAAGARVEVVALDVTDPDAVAALAEAVLARFGPIDVLVNNAGVGGG-GPFEELDLEDLRRVFEVNVFGPVRLTRALL 125

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462538571  82 PYM-ENRRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDF 146
Cdd:COG0300   126 PLMrARGRGRIVNVSSVAGLRGLPGMAAYAASKAALEGFSESLRAELAPTGVRVTAVCPGPVDTPF 191

tropinone reductase-I and II (TR-1, and TR-II)-like, classical (c) SDRs; This subgroup includes TR-I and TR-II; these proteins are members of the SDR family. TRs catalyze the NADPH-dependent reductions of the 3-carbonyl group of tropinone, to a beta-hydroxyl group. TR-I and TR-II produce different stereoisomers from tropinone, TR-I produces tropine (3alpha-hydroxytropane), and TR-II, produces pseudotropine (sigma-tropine, 3beta-hydroxytropane). 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 2462538571   1 MAKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGG-VDFLVCSAGVNPLVGSTLGTSEQiWDKILSVNVKSpALLLSQ 79
Cdd:cd05329    47 LTEWREKGFKVEGSVCDVSSRSERQELMDTVASHFGGkLNILVNNAGTNIRKEAKDYTEED-YSLIMSTNFEA-AYHLSR 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  80 LL-PYME-NRRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESLW 157
Cdd:cd05329   125 LAhPLLKaSGNGNIVFISSVAGVIAVPSGAPYGATKGALNQLTRSLACEWAKDNIRVNAVAPWVIATPLVEPVIQQKENL 204

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 2462538571 158 KNFKEHHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:cd05329   205 DKVIERTPLKRFGEPEEVAALVAFLCMPAASYITGQIIAVDG 246

NADP-dependent 3-hydroxy acid dehydrogenase YdfG [Energy production and conversion]; NADP-dependent 3-hydroxy acid dehydrogenase YdfG is part of the Pathway/BioSystem: Pyrimidine degradation

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571   8 GLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLvGSTLGTSEQIWDKILSVNVKSPALLLSQLLPYM-EN 86
Cdd:COG4221    50 GGRALAVPLDVTDEAAVEAAVAAAVAEFGRLDVLVNNAGVALL-GPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMrAR 128

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  87 RRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFS-KVFHGN-ESLWKNFKEHH 164
Cdd:COG4221   129 GSGHIVNISSIAGLRPYPGGAVYAATKAAVRGLSESLRAELRPTGIRVTVIEPGAVDTEFLdSVFDGDaEAAAAVYEGLE 208

                         170       180
                  ....*....|....*....|
gi 2462538571 165 QLQrigeSEDCAGIVSFLCS 184
Cdd:COG4221   209 PLT----PEDVAEAVLFALT 224

1-cyclohexenylcarbonyl_coenzyme A_reductase (ChcA)_like, classical (c) SDRs; This subgroup contains classical SDR proteins, including members identified as 1-cyclohexenylcarbonyl coenzyme A reductase. ChcA of Streptomyces collinus is implicated in the final reduction step of shikimic acid to ansatrienin. ChcA shows sequence similarity to the SDR family of NAD-binding proteins, but it lacks the conserved Tyr of the characteristic catalytic site. This subgroup also contains the NADH-dependent enoyl-[acyl-carrier-protein(ACP)] reductase FabL from Bacillus subtilis. This enzyme participates in bacterial fatty acid synthesis, in type II fatty-acid synthases and catalyzes the last step in each elongation cycle. 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 2462538571  18 VGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVgSTLGTSEQIWDKILSVNVKSPALLLSQLLPYMENRR-GAVILVSS 96
Cdd:cd05359    57 VSQPQDVEEMFAAVKERFGRLDVLVSNAAAGAFR-PLSELTPAHWDAKMNTNLKALVHCAQQAAKLMRERGgGRIVAISS 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  97 IAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESLWKNFKEHHQLQRIGESEDCA 176
Cdd:cd05359   136 LGSIRALPNYLAVGTAKAALEALVRYLAVELGPRGIRVNAVSPGVIDTDALAHFPNREDLLEAAAANTPAGRVGTPQDVA 215

                         170       180
                  ....*....|....*....|....*..
gi 2462538571 177 GIVSFLCSPDASYVNGENIAV-AGYST 202
Cdd:cd05359   216 DAVGFLCSDAARMITGQTLVVdGGLSI 242

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571   2 AKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVGSTlGTSEQIWDKILSVNVKSPALLLSQLL 81
Cdd:PRK12939   49 AALEAAGGRAHAIAADLADPASVQRFFDAAAAALGGLDGLVNNAGITNSKSAT-ELDIDTWDAVMNVNVRGTFLMLRAAL 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  82 PYM-ENRRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFS---KVFHGNESLw 157
Cdd:PRK12939  128 PHLrDSGRGRIVNLASDTALWGAPKLGAYVASKGAVIGMTRSLARELGGRGITVNAIAPGLTATEATayvPADERHAYY- 206

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 2462538571 158 knfKEHHQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:PRK12939  207 ---LKGRALERLQVPDDVAGAVLFLLSDAARFVTGQLLPVNG 245

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571   6 GEGLSVAgivCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDKILSVNVKSPALLLSQLLPYM- 84
Cdd:PRK06172   56 GEALFVA---CDVTRDAEVKALVEQTIAAYGRLDYAFNNAGIEIEQGRLAEGSEAEFDAIMGVNVKGVWLCMKYQIPLMl 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  85 ENRRGAVILVSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFHGNESLWKNF-KEH 163
Cdd:PRK06172  133 AQGGGAIVNTASVAGLGAAPKMSIYAASKHAVIGLTKSAAIEYAKKGIRVNAVCPAVIDTDMFRRAYEADPRKAEFaAAM 212

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 2462538571 164 HQLQRIGESEDCAGIVSFLCSPDASYVNGENIAVAG 199
Cdd:PRK06172  213 HPVGRIGKVEEVASAVLYLCSDGASFTTGHALMVDG 248

7 alpha-hydroxysteroid dehydrogenase (7 alpha-HSDH), classical (c) SDRs; This bacterial subgroup contains 7 alpha-HSDHs, including Escherichia coli 7 alpha-HSDH. 7 alpha-HSDH, a member of the SDR family, catalyzes the NAD+ -dependent dehydrogenation of a hydroxyl group at position 7 of the steroid skeleton of bile acids. In humans the two primary bile acids are cholic and chenodeoxycholic acids, these are formed from cholesterol in the liver. Escherichia coli 7 alpha-HSDH dehydroxylates these bile acids in the human intestine. Mammalian 7 alpha-HSDH activity has been found in livers. 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 2462538571   2 AKLQGEGLSVAGIVCHVGKAEDREQLVAKALEHCGGVDFLVCSAGVNPLVGSTLGTSEQIWDKILSVNVKSpALLLSQL- 80
Cdd:cd05365    41 AAIQQAGGQAIGLECNVTSEQDLEAVVKATVSQFGGITILVNNAGGGGPKPFDMPMTEEDFEWAFKLNLFS-AFRLSQLc 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538571  81 LPYMENRRGAVIL-VSSIAAYNPVVALGVYNVSKTALLGLTRTLALELAPKDIRVNCVVPGIIKTDFSKVFhGNESLWKN 159
Cdd:cd05365   120 APHMQKAGGGAILnISSMSSENKNVRIAAYGSSKAAVNHMTRNLAFDLGPKGIRVNAVAPGAVKTDALASV-LTPEIERA 198