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 298228987   6 KVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGvkCKAALDEQFEPQKTLFIQCDVADQAQLRDTFRKVVDHFGRL 85
Cdd:cd05323    1 KVAIITGGASGIGLATAKLLLKKGAKVAILDRNENPG--AAAELQAINPKVKATFVQCDVTSWEQLAAAFKKAIEKFGRV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  86 DILVNNAGVNNEK----------NWEKTLQINLVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd05323   79 DILINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASK 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987 156 HGIIGFTRSAAMAANlMNSGVRLNAICPGFVNTPILKSIEKEEnmgqyieytdhiKDMMKYYGVLDPSMIANGLITLIED 235
Cdd:cd05323  159 HGVVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIED 225

                        250
                 ....*....|....*....
gi 298228987 236 DALNGAIMKITTSKGIHFQ 254
Cdd:cd05323  226 DEKNGAIWIVDGGKLIEIE 244

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 298228987   6 KVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGvkCKAALDEQFEPQKTLFIQCDVADQAQLRDTFRKVVDHFGRL 85
Cdd:cd05323    1 KVAIITGGASGIGLATAKLLLKKGAKVAILDRNENPG--AAAELQAINPKVKATFVQCDVTSWEQLAAAFKKAIEKFGRV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  86 DILVNNAGVNNEK----------NWEKTLQINLVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd05323   79 DILINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASK 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987 156 HGIIGFTRSAAMAANlMNSGVRLNAICPGFVNTPILKSIEKEEnmgqyieytdhiKDMMKYYGVLDPSMIANGLITLIED 235
Cdd:cd05323  159 HGVVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIED 225

                        250
                 ....*....|....*....
gi 298228987 236 DALNGAIMKITTSKGIHFQ 254
Cdd:cd05323  226 DEKNGAIWIVDGGKLIEIE 244

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 298228987   5 GKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGVKCKAALDEqfEPQKTLFIQCDVADQAQLRDTFRKVVDHFGR 84
Cdd:COG1028    6 GKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRA--AGGRALAVAADVTDEAAVEALVAAAVAAFGR 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  85 LDILVNNAGVNN--------EKNWEKTLQINLVSVISGTYLGLDYMSKQnggEGGIIINMSSLAGLMPVAQQPVYCASKH 156
Cdd:COG1028   84 LDILVNNAGITPpgpleeltEEDWDRVLDVNLKGPFLLTRAALPHMRER---GGGRIVNISSIAGLRGSPGQAAYAASKA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987 157 GIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSI-EKEENMGQYIEYTDhikdmMKYYGvlDPSMIANGLITLIED 235
Cdd:COG1028  161 AVVGLTRS--LALELAPRGIRVNAVAPGPIDTPMTRALlGAEEVREALAARIP-----LGRLG--TPEEVAAAVLFLASD 231

                        250
                 ....*....|..
gi 298228987 236 DA--LNGAIMKI 245
Cdd:COG1028  232 AAsyITGQVLAV 243

SDR family mycofactocin-dependent oxidoreductase; Members of this protein subfamily are putative oxidoreductases belonging to the larger SDR family. All members occur in genomes that encode a cassette for the biosynthesis of mycofactocin, a proposed electron carrier of a novel redox pool. Characterized members of this family are described as NDMA-dependent, meaning that a blue aniline dye serving as an artificial electron acceptor is required for members of this family to cycle in vitro, since the bound NAD residue is not exchangeable. This family resembles TIGR03971 most closely in the N-terminal region, consistent with the published hypothesis of NAD interaction with mycofactocin. See EC 1.1.99.36. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987    5 GKVALVTGAAQGIGRASAEALLLKGAKVALVDW-NFEAGVKCKAALDEQFE------PQKTLFIQCDVADQAQLRDTFRK 77
Cdd:TIGR04504   1 GRVALVTGAARGIGAATVRRLAADGWRVVAVDLcADDPAVGYPLATRAELDavaaacPDQVLPVIADVRDPAALAAAVAL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987   78 VVDHFGRLDILVNNAGV--NNEKNWEKT-------LQINLVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQ 148
Cdd:TIGR04504  81 AVERWGRLDAAVAAAGViaGGRPLWETTdaeldllLDVNLRGVWNLARAAVPAMLARPDPRGGRFVAVASAAATRGLPHL 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 298228987  149 PVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPIL 191
Cdd:TIGR04504 161 AAYCAAKHAVVGLVRG--LAADLGGTGVTANAVSPGSTRTAML 201

This enzymatic domain is part of bacterial polyketide synthases; It catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987     6 KVALVTGAAQGIGRASAEALLLKGA-KVALV------DWNFEAGVKCKAALDEQfepqkTLFIQCDVADQAQLRDTFRKV 78
Cdd:smart00822   1 GTYLITGGLGGLGRALARWLAERGArRLVLLsrsgpdAPGAAALLAELEAAGAR-----VTVVACDVADRDALAAVLAAI 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987    79 VDHFGRLDILVNNAGVNN--------EKNWEKTLQ------INLVSVISGtyLGLDYMskqnggeggiiINMSSLAGLMP 144
Cdd:smart00822  76 PAVEGPLTGVIHAAGVLDdgvlasltPERFAAVLApkaagaWNLHELTAD--LPLDFF-----------VLFSSIAGVLG 142

                   ....*....
gi 298228987   145 VAQQPVYCA 153
Cdd:smart00822 143 SPGQANYAA 151

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 298228987   6 KVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGvkCKAALDEQFEPQKTLFIQCDVADQAQLRDTFRKVVDHFGRL 85
Cdd:cd05323    1 KVAIITGGASGIGLATAKLLLKKGAKVAILDRNENPG--AAAELQAINPKVKATFVQCDVTSWEQLAAAFKKAIEKFGRV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  86 DILVNNAGVNNEK----------NWEKTLQINLVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd05323   79 DILINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASK 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987 156 HGIIGFTRSAAMAANlMNSGVRLNAICPGFVNTPILKSIEKEEnmgqyieytdhiKDMMKYYGVLDPSMIANGLITLIED 235
Cdd:cd05323  159 HGVVGFTRSLADLLE-YKTGVRVNAICPGFTNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIED 225

                        250
                 ....*....|....*....
gi 298228987 236 DALNGAIMKITTSKGIHFQ 254
Cdd:cd05323  226 DEKNGAIWIVDGGKLIEIE 244

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987   8 ALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGvkcKAALDEQFEPQKTLFIQCDVADQAQLRDTFRKVVDHFGRLDI 87
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEAL---AELAAIEALGGNAVAVQADVSDEEDVEALVEEALEEFGRLDI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  88 LVNNAGVN--------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNGGeggIIINMSSLAGLMPVAQQPVYCASKHGII 159
Cdd:cd05233   78 LVNNAGIArpgpleelTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGG---RIVNISSVAGLRPLPGQAAYAASKAALE 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987 160 GFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSIEKEENMGQYIEYTDHIKdmmkyygVLDPSMIANGLITLIEDDA-- 237
Cdd:cd05233  155 GLTRS--LALELAPYGIRVNAVAPGLVDTPMLAKLGPEEAEKELAAAIPLGR-------LGTPEEVAEAVVFLASDEAsy 225

                 ....*....
gi 298228987 238 LNGAIMKIT 246
Cdd:cd05233  226 ITGQVIPVD 234

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 298228987   1 MHVNGKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGVKCKAALDEQFepqktLFIQCDVADQAQLRDTFRKVVD 80
Cdd:COG4221    1 MSDKGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAELGGRA-----LAVPLDVTDEAAVEAAVAAAVA 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  81 HFGRLDILVNNAGVN--------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNggeGGIIINMSSLAGLMPVAQQPVYC 152
Cdd:COG4221   76 EFGRLDVLVNNAGVAllgpleelDPEDWDRMIDVNVKGVLYVTRAALPAMRARG---SGHIVNISSIAGLRPYPGGAVYA 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987 153 ASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSIEKEENMGQYIEYTDhikdmmkyYGVLDPSMIANGLITL 232
Cdd:COG4221  153 ATKAAVRGLSES--LRAELRPTGIRVTVIEPGAVDTEFLDSVFDGDAEAAAAVYEG--------LEPLTPEDVAEAVLFA 222

                 ....*
gi 298228987 233 IEDDA 237
Cdd:COG4221  223 LTQPA 227

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987   1 MHVNGKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGVKCKAALDEQFEpqKTLFIQCDVADQAQLRDTFRKVVD 80
Cdd:PRK05653   1 MSLQGKTALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRAAGG--EARVLVFDVSDEAAVRALIEAAVE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  81 HFGRLDILVNNAGVNN--------EKNWEKTLQINLvsviSGTYLG----LDYMSKQNGGEggiIINMSSLAGLMPVAQQ 148
Cdd:PRK05653  79 AFGALDILVNNAGITRdallprmsEEDWDRVIDVNL----TGTFNVvraaLPPMIKARYGR---IVNISSVSGVTGNPGQ 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 298228987 149 PVYCASKHGIIGFTRSAAMaaNLMNSGVRLNAICPGFVNTPILKSIEKE 197
Cdd:PRK05653 152 TNYSAAKAGVIGFTKALAL--ELASRGITVNAVAPGFIDTDMTEGLPEE 198

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987   1 MHVNGKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGvkcKAALDEQFEPQKTLFIQCDVADQAQLRDTFRKVVD 80
Cdd:PRK07231   1 MRLEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAA---ERVAAEILAGGRAIAVAADVSDEADVEAAVAAALE 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  81 HFGRLDILVNNAGVN---------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNggeGGIIINMSSLAGLMPVAQQPVY 151
Cdd:PRK07231  78 RFGSVDILVNNAGTThrngplldvDEAEFDRIFAVNVKSPYLWTQAAVPAMRGEG---GGAIVNVASTAGLRPRPGLGWY 154

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 298228987 152 CASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKS 193
Cdd:PRK07231 155 NASKGAVITLTKA--LAAELGPDKIRVNAVAPVVVETGLLEA 194

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987   5 GKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGvkckAALDEQFEPQ--KTLFIQCDVADQAQLRDTFRKVVDHF 82
Cdd:PRK12826   6 GRVALVTGAARGIGRAIAVRLAADGAEVIVVDICGDDA----AATAELVEAAggKARARQVDVRDRAALKAAVAAGVEDF 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  83 GRLDILVNNAGVNN--------EKNWEKTLQINLVSVISGTYLGLDYMSKQNGGEggiIINMSSLAGL-MPVAQQPVYCA 153
Cdd:PRK12826  82 GRLDILVANAGIFPltpfaemdDEQWERVIDVNLTGTFLLTQAALPALIRAGGGR---IVLTSSVAGPrVGYPGLAHYAA 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987 154 SKHGIIGFTRSAAMaaNLMNSGVRLNAICPGFVNTPILksiekeENMGQyIEYTDHIKDMMKYYGVLDPSMIANGLITLI 233
Cdd:PRK12826 159 SKAGLVGFTRALAL--ELAARNITVNSVHPGGVDTPMA------GNLGD-AQWAEAIAAAIPLGRLGEPEDIAAAVLFLA 229

                        250
                 ....*....|....
gi 298228987 234 EDDA--LNGAIMKI 245
Cdd:PRK12826 230 SDEAryITGQTLPV 243

3beta17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; This subgroup includes members identified as 3beta17beta hydroxysteroid dehydrogenase, 20beta hydroxysteroid dehydrogenase, and R-alcohol dehydrogenase. These proteins exhibit the canonical active site tetrad and glycine rich NAD(P)-binding motif of the classical SDRs. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. 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 298228987   3 VNGKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGVKCKAALDEQfepqkTLFIQCDVADQAQLRDTFRKVVDHF 82
Cdd:cd05341    3 LKGKVAIVTGGARGLGLAHARLLVAEGAKVVLSDILDEEGQAAAAELGDA-----ARFFHLDVTDEDGWTAVVDTAREAF 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  83 GRLDILVNNAGVNNEKN--------WEKTLQINLVSVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCAS 154
Cdd:cd05341   78 GRLDVLVNNAGILTGGTvetttleeWRRLLDINLTGVFLGTRAVIPPMKEAGGGS---IINMSSIEGLVGDPALAAYNAS 154

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 298228987 155 KHGIIGFTRSAAMAANLMNSGVRLNAICPGFVNTPILKSI-EKEENMGQY 203
Cdd:cd05341  155 KGAVRGLTKSAALECATQGYGIRVNSVHPGYIYTPMTDELlIAQGEMGNY 204

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 298228987   6 KVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEagvKCKAALDEQFE-PQKTLFIQCDVADQAQLRDTFRKVVDHFGR 84
Cdd:cd05333    1 KVALVTGASRGIGRAIALRLAAEGAKVAVTDRSEE---AAAETVEEIKAlGGNAAALEADVSDREAVEALVEKVEAEFGP 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  85 LDILVNNAGVN--------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKH 156
Cdd:cd05333   78 VDILVNNAGITrdnllmrmSEEDWDAVINVNLTGVFNVTQAVIRAMIKRRSGR---IINISSVVGLIGNPGQANYAASKA 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987 157 GIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSIEKeenmgqyiEYTDHIKDM--MKYYGvlDPSMIANGLITLIE 234
Cdd:cd05333  155 GVIGFTKS--LAKELASRGITVNAVAPGFIDTDMTDALPE--------KVKEKILKQipLGRLG--TPEEVANAVAFLAS 222

                 ...
gi 298228987 235 DDA 237
Cdd:cd05333  223 DDA 225

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 298228987   4 NGKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGVKCKAALDEQFEpQKTLFIQCDVADQAQLRDTFRKVVDHFG 83
Cdd:cd05366    1 MSKVAIITGAAQGIGRAIAERLAADGFNIVLADLNLEEAAKSTIQEISEAG-YNAVAVGADVTDKDDVEALIDQAVEKFG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  84 RLDILVNNAGVN--------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNGgeGGIIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd05366   80 SFDVMVNNAGIApitplltiTEEDLKKVYAVNVFGVLFGIQAAARQFKKLGH--GGKIINASSIAGVQGFPNLGAYSASK 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 298228987 156 HGIIGFTRSAamAANLMNSGVRLNAICPGFVNTPILKSIEKEE 198
Cdd:cd05366  158 FAVRGLTQTA--AQELAPKGITVNAYAPGIVKTEMWDYIDEEV 198

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987   1 MHVNGKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGVKCKAALDEQfePQKTLFIQCDVADQAQLRDTFRKVVD 80
Cdd:PRK06172   3 MTFSGKVALVTGGAAGIGRATALAFAREGAKVVVADRDAAGGEETVALIREA--GGEALFVACDVTRDAEVKALVEQTIA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  81 HFGRLDILVNNAGV---------NNEKNWEKTLQINLvsviSGTYLGLDY----MSKQNGGEggiIINMSSLAGLMPVAQ 147
Cdd:PRK06172  81 AYGRLDYAFNNAGIeieqgrlaeGSEAEFDAIMGVNV----KGVWLCMKYqiplMLAQGGGA---IVNTASVAGLGAAPK 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 298228987 148 QPVYCASKHGIIGFTRSAAMaaNLMNSGVRLNAICPGFVNT 188
Cdd:PRK06172 154 MSIYAASKHAVIGLTKSAAI--EYAKKGIRVNAVCPAVIDT 192

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987   3 VNGKVALVTGAAQGIGRASAEALLLKGAKVALVDWNFEAGVKCKAALDeqfepqKTLFIQCDVADQAQLRDTFRKVVDHF 82
Cdd:PRK07825   3 LRGKVVAITGGARGIGLATARALAALGARVAIGDLDEALAKETAAELG------LVVGGPLDVTDPASFAAFLDAVEADL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  83 GRLDILVNNAGV--------NNEKNWEKTLQINLVSVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCAS 154
Cdd:PRK07825  77 GPIDVLVNNAGVmpvgpfldEPDAVTRRILDVNVYGVILGSKLAAPRMVPRGRGH---VVNVASLAGKIPVPGMATYCAS 153

                        170       180       190
                 ....*....|....*....|....*....|....
gi 298228987 155 KHGIIGFTRSAamAANLMNSGVRLNAICPGFVNT 188
Cdd:PRK07825 154 KHAVVGFTDAA--RLELRGTGVHVSVVLPSFVNT 185

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987   4 NGKVALVTGAAQGIGRASAEALLLKGAKVALVDWNfEAGVKCKAALDeqfePQKTLFIQCDVADQAQLRDTFRKVVDHFG 83
Cdd:PRK06841  14 SGKVAVVTGGASGIGHAIAELFAAKGARVALLDRS-EDVAEVAAQLL----GGNAKGLVCDVSDSQSVEAAVAAVISAFG 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 298228987  84 RLDILVNNAGVN--------NEKNWEKTLQINLvsviSGTYLgldyMSKQNGGE-----GGIIINMSSLAGLMPVAQQPV 150
Cdd:PRK06841  89 RIDILVNSAGVAllapaedvSEEDWDKTIDINL----KGSFL----MAQAVGRHmiaagGGKIVNLASQAGVVALERHVA 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 298228987 151 YCASKHGIIGFTRsaAMAANLMNSGVRLNAICPGFVNTPILK---SIEKEENMGQYI 204
Cdd:PRK06841 161 YCASKAGVVGMTK--VLALEWGPYGITVNAISPTVVLTELGKkawAGEKGERAKKLI 215