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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFG-LTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDI 90
Cdd:cd05324     2 VALVTGANRGIGFEIVRQLAKSGpGTVILTARDVERGQAAVEKLRAEGLSVRFHQLDVTDDASIEAAADFVEEKYGGLDI 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1175889628  91 LVNNAGVSFSEI--HSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPAmkSRVLNISSQLALQT 153
Cdd:cd05324    82 LVNNAGIAFKGFddSTPTREQARETMKTNFFGTVDVTQALLPLLKKSPA--GRIVNVSSGLGSLT 144

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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFG-LTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDI 90
Cdd:cd05324     2 VALVTGANRGIGFEIVRQLAKSGpGTVILTARDVERGQAAVEKLRAEGLSVRFHQLDVTDDASIEAAADFVEEKYGGLDI 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1175889628  91 LVNNAGVSFSEI--HSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPAmkSRVLNISSQLALQT 153
Cdd:cd05324    82 LVNNAGIAFKGFddSTPTREQARETMKTNFFGTVDVTQALLPLLKKSPA--GRIVNVSSGLGSLT 144

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:pfam00106   2 VALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQAVERLGRLDIL 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1175889628  92 VNNAGVS-FSEIHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPamKSRVLNISSQLALQ 152
Cdd:pfam00106  82 VNNAGITgLGPFSELSDEDWERVIDVNLTGVFNLTRAVLPAMIKGS--GGRIVNISSVAGLV 141

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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTC-RSESKGVEAVLSL-AKRGLTAHFCKLDVTDDESILNFASRL----HVTF 85
Cdd:TIGR02685   3 AAVVTGAAKRIGSSIAVALHQEGYRVVLHYhRSAAAASTLAAELnARRPNSAVTCQADLSNSATLFSRCEAIidacFRAF 82

                          90
                  ....*....|
gi 1175889628  86 GGLDILVNNA 95
Cdd:TIGR02685  83 GRCDVLVNNA 92

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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFG-LTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDI 90
Cdd:cd05324     2 VALVTGANRGIGFEIVRQLAKSGpGTVILTARDVERGQAAVEKLRAEGLSVRFHQLDVTDDASIEAAADFVEEKYGGLDI 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1175889628  91 LVNNAGVSFSEI--HSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPAmkSRVLNISSQLALQT 153
Cdd:cd05324    82 LVNNAGIAFKGFddSTPTREQARETMKTNFFGTVDVTQALLPLLKKSPA--GRIVNVSSGLGSLT 144

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:COG0300     7 TVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAGARVEVVALDVTDPDAVAALAEAVLARFGPIDVL 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1175889628  92 VNNAGVS-FSEIHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPamKSRVLNISSQLALQ 152
Cdd:COG0300    87 VNNAGVGgGGPFEELDLEDLRRVFEVNVFGPVRLTRALLPLMRARG--RGRIVNVSSVAGLR 146

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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLakrGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:COG4221     7 VALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAEL---GGRALAVPLDVTDEAAVEAAVAAAVAEFGRLDVL 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1175889628  92 VNNAGVS-FSEIHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPamKSRVLNISS 147
Cdd:COG4221    84 VNNAGVAlLGPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRARG--SGHIVNISS 138

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:PRK12939    9 RALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAAGGRAHAIAADLADPASVQRFFDAAAAALGGLDGL 88

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1175889628  92 VNNAGVsfseIHSNNVEEAEI-----VIRTNFYGQRKLIQELLPLFRRSPamKSRVLNISSQLALQTG 154
Cdd:PRK12939   89 VNNAGI----TNSKSATELDIdtwdaVMNVNVRGTFLMLRAALPHLRDSG--RGRIVNLASDTALWGA 150

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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKgVEAVLSLAKRGLTAhfCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:cd05374     2 VVLITGCSSGIGLALALALAAQGYRVIATARNPDK-LESLGELLNDNLEV--LELDVTDEESIKAAVKEVIERFGRIDVL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1175889628  92 VNNAGVS-FSEIHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPamKSRVLNISSQLALQT 153
Cdd:cd05374    79 VNNAGYGlFGPLEETSIEEVRELFEVNVFGPLRVTRAFLPLMRKQG--SGRIVNVSSVAGLVP 139

Short-chain dehydrogenase involved in D-alanine esterification of teichoic acids [Cell wall/membrane/envelope biogenesis, Lipid transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628   7 WTEKTVAIvTGANRGIGFAIVEKLAEFGLTVVLTCRSESKgveavLSLAKRGL-TAHFCKLDVTDDESILNFASRLHVTF 85
Cdd:COG3967     3 LTGNTILI-TGGTSGIGLALAKRLHARGNTVIITGRREEK-----LEEAAAANpGLHTIVLDVADPASIAALAEQVTAEF 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1175889628  86 GGLDILVNNAGVSFSE---IHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPAmkSRVLNISSQLAL 151
Cdd:COG3967    77 PDLNVLINNAGIMRAEdllDEAEDLADAEREITTNLLGPIRLTAAFLPHLKAQPE--AAIVNVSSGLAF 143

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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:cd05333     2 VALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEIKALGGNAAALEADVSDREAVEALVEKVEAEFGPVDIL 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1175889628  92 VNNAGVS-------FSEihsnnvEEAEIVIRTNFYGQRKLIQELLPLFRRspAMKSRVLNISS 147
Cdd:cd05333    82 VNNAGITrdnllmrMSE------EDWDAVINVNLTGVFNVTQAVIRAMIK--RRSGRIINISS 136

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:PRK12826    8 VALVTGAARGIGRAIAVRLAADGAEVIVVDICGDDAAATAELVEAAGGKARARQVDVRDRAALKAAVAAGVEDFGRLDIL 87

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  92 VNNAGVS----FSEIhsnNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPAmkSRVLNISS 147
Cdd:PRK12826   88 VANAGIFpltpFAEM---DDEQWERVIDVNLTGTFLLTQAALPALIRAGG--GRIVLTSS 142

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  17 GA--NRGIGFAIVEKLAEFGLTVVLTCRSEsKGVEAVLSLAKRgLTAHFCKLDVTDDESILNFASRLHVTFGGLDILVNN 94
Cdd:pfam13561   1 GAanESGIGWAIARALAEEGAEVVLTDLNE-ALAKRVEELAEE-LGAAVLPCDVTDEEQVEALVAAAVEKFGRLDILVNN 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1175889628  95 AGVS---FSEIHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRspamKSRVLNISSQLALQ 152
Cdd:pfam13561  79 AGFApklKGPFLDTSREDFDRALDVNLYSLFLLAKAALPLMKE----GGSIVNLSSIGAER 135

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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:cd05347     7 VALVTGASRGIGFGIASGLAEAGANIVINSRNEEKAEEAQQLIEKEGVEATAFTCDVSDEEAIKAAVEAIEEDFGKIDIL 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1175889628  92 VNNAGVsfseIHSNNVEEAEI-----VIRTNFYGQRKLIQELLPLFRRSPAMKsrVLNISSQLALQTGD 155
Cdd:cd05347    87 VNNAGI----IRRHPAEEFPEaewrdVIDVNLNGVFFVSQAVARHMIKQGHGK--IINICSLLSELGGP 149

short chain dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628   8 TEKTVAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSeskgVEAVLSLAKRGltAHFCKLDVTDDESILNFASRLHVTFGG 87
Cdd:PRK06182    1 MQKKVALVTGASSGIGKATARRLAAQGYTVYGAARR----VDKMEDLASLG--VHPLSLDVTDEASIKAAVDTIIAEEGR 74

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1175889628  88 LDILVNNAGV-SFSEIHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRrspAMKS-RVLNISS 147
Cdd:PRK06182   75 IDVLVNNAGYgSYGAIEDVPIDEARRQFEVNLFGAARLTQLVLPHMR---AQRSgRIINISS 133

gluconate 5-dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:PRK08213   14 TALVTGGSRGLGLQIAEALGEAGARVVLSARKAEELEEAAAHLEALGIDALWIAADVADEADIERLAEETLERFGHVDIL 93

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1175889628  92 VNNAGVSF---SEIHSnnVEEAEIVIRTNFYGQRKLIQELLplfRRS--PAMKSRVLNISSQLALQTGD 155
Cdd:PRK08213   94 VNNAGATWgapAEDHP--VEAWDKVMNLNVRGLFLLSQAVA---KRSmiPRGYGRIINVASVAGLGGNP 157

glucose 1 dehydrogenase (GlcDH), classical (c) SDRs; GlcDH, is a tetrameric member of the SDR family, it catalyzes the NAD(P)-dependent oxidation of beta-D-glucose to D-glucono-delta-lactone. GlcDH has a typical NAD-binding site glycine-rich pattern as well as the canonical active site tetrad (YXXXK motif plus upstream Ser and Asn). 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 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKR-GLTAHFCKLDVTDDESILNFASRLHVTFGGLDI 90
Cdd:cd05358     5 VALVTGASSGIGKAIAIRLATAGANVVVNYRSKEDAAEEVVEEIKAvGGKAIAVQADVSKEEDVVALFQSAIKEFGTLDI 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1175889628  91 LVNNAGVSFSE-IHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPAmKSRVLNISS 147
Cdd:cd05358    85 LVNNAGLQGDAsSHEMTLEDWNKVIDVNLTGQFLCAREAIKRFRKSKI-KGKIINMSS 141

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  15 VTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDILVNN 94
Cdd:PRK05650    5 ITGAASGLGRAIALRWAREGWRLALADVNEEGGEETLKLLREAGGDGFYQRCDVRDYSQLTALAQACEEKWGGIDVIVNN 84

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1175889628  95 AGV----SFSEIhsnNVEEAEIVIRTNFYGQRKLIQELLPLFRRSPAmkSRVLNISSQLAL 151
Cdd:PRK05650   85 AGVasggFFEEL---SLEDWDWQIAINLMGVVKGCKAFLPLFKRQKS--GRIVNIASMAGL 140

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:PRK07201  373 VVLITGASSGIGRATAIKVAEAGATVFLVARNGEALDELVAEIRAKGGTAHAYTCDLTDSAAVDHTVKDILAEHGHVDYL 452

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1175889628  92 VNNAGVSF--SEIHS-NNVEEAEIVIRTNFYGQRKLIQELLplfrrsPAMKSR----VLNISSQlALQT 153
Cdd:PRK07201  453 VNNAGRSIrrSVENStDRFHDYERTMAVNYFGAVRLILGLL------PHMRERrfghVVNVSSI-GVQT 514

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 1175889628   8 TEKTVaIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKgVEAVLS--LAKRGLTAHFCKLDVTDDESILNFASRLHVTF 85
Cdd:cd05332     2 QGKVV-IITGASSGIGEELAYHLARLGARLVLSARREER-LEEVKSecLELGAPSPHVVPLDMSDLEDAEQVVEEALKLF 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1175889628  86 GGLDILVNNAGVS-FSEIHSNNVEEAEIVIRTNFYGQRKLIQELLP-LFRRSpamKSRVLNISS 147
Cdd:cd05332    80 GGLDILINNAGISmRSLFHDTSIDVDRKIMEVNYFGPVALTKAALPhLIERS---QGSIVVVSS 140

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSEsKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDIL 91
Cdd:PRK07231    7 VAIVTGASSGIGEGIARRFAAEGARVVVTDRNE-EAAERVAAEILAGGRAIAVAADVSDEADVEAAVAAALERFGSVDIL 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1175889628  92 VNNAGVSfseiHSN----NVEEAEI--VIRTNFYGQRKLIQELLPLFRRspAMKSRVLNISS 147
Cdd:PRK07231   86 VNNAGTT----HRNgpllDVDEAEFdrIFAVNVKSPYLWTQAAVPAMRG--EGGGAIVNVAS 141

3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628   9 EKTVAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESI---LNFASRlhvTF 85
Cdd:PRK12429    3 KGKVALVTGAASGIGLEIALALAKEGAKVVIADLNDEAAAAAAEALQKAGGKAIGVAMDVTDEEAInagIDYAVE---TF 79

                          90       100
                  ....*....|....*....|....
gi 1175889628  86 GGLDILVNNAGVSfseiHSNNVEE 109
Cdd:PRK12429   80 GGVDILVNNAGIQ----HVAPIED 99

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  13 AIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKGVEAVLSLAKRgltAHFCKLDVTDDESILNFASRLHVTFGGLDILV 92
Cdd:cd08929     3 ALVTGASRGIGEATARLLHAEGYRVGICARDEARLAAAAAQELEG---VLGLAGDVRDEADVRRAVDAMEEAFGGLDALV 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  93 NNAGVS-FSEIHSNNVEEAEIVIRTN----FYGQRKLIqelLPLFRRSPAMksrVLNISS 147
Cdd:cd08929    80 NNAGVGvMKPVEELTPEEWRLVLDTNltgaFYCIHKAA---PALLRRGGGT---IVNVGS 133

meso-2,3-butanediol dehydrogenase-like, classical (c) SDRs; 2,3-butanediol dehydrogenases (BDHs) catalyze the NAD+ dependent conversion of 2,3-butanediol to acetonin; BDHs are classified into types according to their stereospecificity as to substrates and products. Included in this subgroup are Klebsiella pneumonia meso-BDH which catalyzes meso-2,3-butanediol to D(-)-acetonin, and Corynebacterium glutamicum L-BDH which catalyzes lX+)-2,3-butanediol to L(+)-acetonin. This subgroup is comprised of classical SDRs with the characteristic catalytic triad and NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLT-CRSESKGVEAVLSLAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDI 90
Cdd:cd05366     4 VAIITGAAQGIGRAIAERLAADGFNIVLAdLNLEEAAKSTIQEISEAGYNAVAVGADVTDKDDVEALIDQAVEKFGSFDV 83

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1175889628  91 LVNNAGVSFSE-IHSNNVEEAEIVIRTNFYGQRKLIQELLPLFRRSpAMKSRVLNISSQLALQ 152
Cdd:cd05366    84 MVNNAGIAPITpLLTITEEDLKKVYAVNVFGVLFGIQAAARQFKKL-GHGGKIINASSIAGVQ 145

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1175889628  12 VAIVTGANRGIGFAIVEKLAEFGLTVVLTCRSESKgVEAVLS-LAKRGLTAHFCKLDVTDDESILNFASRLHVTFGGLDI 90
Cdd:PRK07666    9 NALITGAGRGIGRAVAIALAKEGVNVGLLARTEEN-LKAVAEeVEAYGVKVVIATADVSDYEEVTAAIEQLKNELGSIDI 87

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1175889628  91 LVNNAGVS-FSEIHSNNVEEAEIVIRTNFYGQRKLIQELLplfrrsPAMKSR----VLNISS 147
Cdd:PRK07666   88 LINNAGISkFGKFLELDPAEWEKIIQVNLMGVYYATRAVL------PSMIERqsgdIINISS 143