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 224922801   6 KVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGvqCKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVDHFGRL 85
Cdd:cd05323    1 KVAIITGGASGIGLATAKLLLKKGAKVAILDRNENPG--AAAELQAINPKVKATFVQCDVTSWEQLAAAFKKAIEKFGRV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  86 DILVNNAGVNNEK----------NWEKTLQINLVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd05323   79 DILINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASK 158

                        170
                 ....*....|...
gi 224922801 156 HGIVGFTRSAAPT 168
Cdd:cd05323  159 HGVVGFTRSLADL 171

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 224922801   6 KVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGvqCKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVDHFGRL 85
Cdd:cd05323    1 KVAIITGGASGIGLATAKLLLKKGAKVAILDRNENPG--AAAELQAINPKVKATFVQCDVTSWEQLAAAFKKAIEKFGRV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  86 DILVNNAGVNNEK----------NWEKTLQINLVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd05323   79 DILINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASK 158

                        170
                 ....*....|...
gi 224922801 156 HGIVGFTRSAAPT 168
Cdd:cd05323  159 HGVVGFTRSLADL 171

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 224922801   5 GKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEqfEPQKTLFIQCDVADQQQLRDTFRKVVDHFGR 84
Cdd:COG1028    6 GKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRA--AGGRALAVAADVTDEAAVEALVAAAVAAFGR 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  85 LDILVNNAGVNN--------EKNWEKTLQINLVSVISGTYLGLDYMSKQnggEGGIIINMSSLAGLMPVAQQPVYCASKH 156
Cdd:COG1028   84 LDILVNNAGITPpgpleeltEEDWDRVLDVNLKGPFLLTRAALPHMRER---GGGRIVNISSIAGLRGSPGQAAYAASKA 160

                        170
                 ....*....|
gi 224922801 157 GIVGFTRSAA 166
Cdd:COG1028  161 AVVGLTRSLA 170

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 224922801    5 GKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNL-EAGVQCKAALDEQFE------PQKTLFIQCDVADQQQLRDTFRK 77
Cdd:TIGR04504   1 GRVALVTGAARGIGAATVRRLAADGWRVVAVDLCAdDPAVGYPLATRAELDavaaacPDQVLPVIADVRDPAALAAAVAL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   78 VVDHFGRLDILVNNAGV---------NNEKNWEKTLQINLVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQ 148
Cdd:TIGR04504  81 AVERWGRLDAAVAAAGViaggrplweTTDAELDLLLDVNLRGVWNLARAAVPAMLARPDPRGGRFVAVASAAATRGLPHL 160

                         170
                  ....*....|....*...
gi 224922801  149 PVYCASKHGIVGFTRSAA 166
Cdd:TIGR04504 161 AAYCAAKHAVVGLVRGLA 178

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 224922801     6 KVALVTGAAQGIGRAFAEALLLKGA-KVALV------DWNLEAGVQCKAALDEQfepqkTLFIQCDVADQQQLRDTFRKV 78
Cdd:smart00822   1 GTYLITGGLGGLGRALARWLAERGArRLVLLsrsgpdAPGAAALLAELEAAGAR-----VTVVACDVADRDALAAVLAAI 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801    79 VDHFGRLDILVNNAGVNN--------EKNWEKTLQ------INLVSVISGtyLGLDYMskqnggeggiiINMSSLAGLMP 144
Cdd:smart00822  76 PAVEGPLTGVIHAAGVLDdgvlasltPERFAAVLApkaagaWNLHELTAD--LPLDFF-----------VLFSSIAGVLG 142

                   ....*....
gi 224922801   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 224922801   6 KVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGvqCKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVDHFGRL 85
Cdd:cd05323    1 KVAIITGGASGIGLATAKLLLKKGAKVAILDRNENPG--AAAELQAINPKVKATFVQCDVTSWEQLAAAFKKAIEKFGRV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  86 DILVNNAGVNNEK----------NWEKTLQINLVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd05323   79 DILINNAGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASK 158

                        170
                 ....*....|...
gi 224922801 156 HGIVGFTRSAAPT 168
Cdd:cd05323  159 HGVVGFTRSLADL 171

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 224922801   8 ALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGvqcKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVDHFGRLDI 87
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEAL---AELAAIEALGGNAVAVQADVSDEEDVEALVEEALEEFGRLDI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  88 LVNNAGVNN--------EKNWEKTLQINLVSVISGTYLGLDYMSKQNGGeggIIINMSSLAGLMPVAQQPVYCASKHGIV 159
Cdd:cd05233   78 LVNNAGIARpgpleeltDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGG---RIVNISSVAGLRPLPGQAAYAASKAALE 154

                 ....*..
gi 224922801 160 GFTRSAA 166
Cdd:cd05233  155 GLTRSLA 161

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 224922801   1 MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQFepqktLFIQCDVADQQQLRDTFRKVVD 80
Cdd:COG4221    1 MSDKGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAELGGRA-----LAVPLDVTDEAAVEAAVAAAVA 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  81 HFGRLDILVNNAGVN--------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNggeGGIIINMSSLAGLMPVAQQPVYC 152
Cdd:COG4221   76 EFGRLDVLVNNAGVAllgpleelDPEDWDRMIDVNVKGVLYVTRAALPAMRARG---SGHIVNISSIAGLRPYPGGAVYA 152

                        170
                 ....*....|....
gi 224922801 153 ASKHGIVGFTRSAA 166
Cdd:COG4221  153 ATKAAVRGLSESLR 166

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   1 MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEqfEPQKTLFIQCDVADQQQLRDTFRKVVD 80
Cdd:COG0300    1 MSLTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRA--AGARVEVVALDVTDPDAVAALAEAVLA 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  81 HFGRLDILVNNAGVN--------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNggeGGIIINMSSLAGLMPVAQQPVYC 152
Cdd:COG0300   79 RFGPIDVLVNNAGVGgggpfeelDLEDLRRVFEVNVFGPVRLTRALLPLMRARG---RGRIVNVSSVAGLRGLPGMAAYA 155

                        170
                 ....*....|....
gi 224922801 153 ASKHGIVGFTRSAA 166
Cdd:COG0300  156 ASKAALEGFSESLR 169

3-hydroxybutyrate dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   3 VNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVqcKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVDHF 82
Cdd:PRK12429   2 LKGKVALVTGAASGIGLEIALALAKEGAKVVIADLNDEAAA--AAAEALQKAGGKAIGVAMDVTDEEAINAGIDYAVETF 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  83 GRLDILVNNAG---VNN------EKnWEKTLQINLVSVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCA 153
Cdd:PRK12429  80 GGVDILVNNAGiqhVAPiedfptEK-WKKMIAIMLDGAFLTTKAALPIMKAQGGGR---IINMASVHGLVGSAGKAAYVS 155

                        170
                 ....*....|...
gi 224922801 154 SKHGIVGFTRSAA 166
Cdd:PRK12429 156 AKHGLIGLTKVVA 168

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 224922801   3 VNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQfepqkTLFIQCDVADQQQLRDTFRKVVDHF 82
Cdd:cd05341    3 LKGKVAIVTGGARGLGLAHARLLVAEGAKVVLSDILDEEGQAAAAELGDA-----ARFFHLDVTDEDGWTAVVDTAREAF 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  83 GRLDILVNNAGVNNEKN--------WEKTLQINLVSVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCAS 154
Cdd:cd05341   78 GRLDVLVNNAGILTGGTvetttleeWRRLLDINLTGVFLGTRAVIPPMKEAGGGS---IINMSSIEGLVGDPALAAYNAS 154

                        170
                 ....*....|....*..
gi 224922801 155 KHGIVGFTRSAAptIDC 171
Cdd:cd05341  155 KGAVRGLTKSAA--LEC 169

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   1 MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGvqcKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVD 80
Cdd:PRK07231   1 MRLEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAA---ERVAAEILAGGRAIAVAADVSDEADVEAAVAAALE 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  81 HFGRLDILVNNAGVN---------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNggeGGIIINMSSLAGLMPVAQQPVY 151
Cdd:PRK07231  78 RFGSVDILVNNAGTThrngplldvDEAEFDRIFAVNVKSPYLWTQAAVPAMRGEG---GGAIVNVASTAGLRPRPGLGWY 154

                        170
                 ....*....|....*
gi 224922801 152 CASKHGIVGFTRSAA 166
Cdd:PRK07231 155 NASKGAVITLTKALA 169

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   1 MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVAL-VDWNLEAGVQCKAALDEqfEPQKTLFIQCDVADQQQLRDTFRKVV 79
Cdd:PRK05565   1 MKLMGKVAIVTGASGGIGRAIAELLAKEGAKVVIaYDINEEAAQELLEEIKE--EGGDAIAVKADVSSEEDVENLVEQIV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  80 DHFGRLDILVNNAGVNN--------EKNWEKTLQINLVSVISGTYLGLDYMSKQNggeGGIIINMSSLAGLMPVAQQPVY 151
Cdd:PRK05565  79 EKFGKIDILVNNAGISNfglvtdmtDEEWDRVIDVNLTGVMLLTRYALPYMIKRK---SGVIVNISSIWGLIGASCEVLY 155

                        170
                 ....*....|....*
gi 224922801 152 CASKHGIVGFTRSAA 166
Cdd:PRK05565 156 SASKGAVNAFTKALA 170

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   1 MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAgvqCKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVD 80
Cdd:PRK07326   2 MSLKGKVALITGGSKGIGFAIAEALLAEGYKVAITARDQKE---LEEAAAELNNKGNVLGLAADVRDEADVQRAVDAIVA 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  81 HFGRLDILVNNAGVNNEKN--------WEKTLQINLVSVISGTYLGLDYMSKQnggeGGIIINMSSLAGLMPVAQQPVYC 152
Cdd:PRK07326  79 AFGGLDVLIANAGVGHFAPveeltpeeWRLVIDTNLTGAFYTIKAAVPALKRG----GGYIINISSLAGTNFFAGGAAYN 154

                        170
                 ....*....|...
gi 224922801 153 ASKHGIVGFTRSA 165
Cdd:PRK07326 155 ASKFGLVGFSEAA 167

L-iditol 2-dehydrogenase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   1 MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQfepqkTLFIQCDVADQQQLRDTFRKVVD 80
Cdd:PRK07067   2 MRLQGKVALLTGAASGIGEAVAERYLAEGARVVIADIKPARARLAALEIGPA-----AIAVSLDVTRQDSIDRIVAAAVE 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  81 HFGRLDILVNNAGV--------NNEKNWEKTLQINlvsvISGTYLGLDYMSKQ--NGGEGGIIINMSSLAGLMPVAQQPV 150
Cdd:PRK07067  77 RFGGIDILFNNAALfdmapildISRDSYDRLFAVN----VKGLFFLMQAVARHmvEQGRGGKIINMASQAGRRGEALVSH 152

                        170
                 ....*....|....*.
gi 224922801 151 YCASKHGIVGFTRSAA 166
Cdd:PRK07067 153 YCATKAAVISYTQSAA 168

d-3-hydroxybutyrate dehydrogenase (HBDH), classical (c) SDRs; DHBDH, an NAD+ -dependent enzyme, catalyzes the interconversion of D-3-hydroxybutyrate and acetoacetate. It is a classical SDR, with the canonical NAD-binding motif and active site tetrad. 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 224922801   4 NGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVDHFG 83
Cdd:cd08940    1 KGKVALVTGSTSGIGLGIARALAAAGANIVLNGFGDAAEIEAVRAGLAAKHGVKVLYHGADLSKPAAIEDMVAYAQRQFG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  84 RLDILVNNAGVNN--------EKNWEKTLQINLVSVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd08940   81 GVDILVNNAGIQHvapiedfpTEKWDAIIALNLSAVFHTTRLALPHMKKQGWGR---IINIASVHGLVASANKSAYVAAK 157

                        170
                 ....*....|.
gi 224922801 156 HGIVGFTRSAA 166
Cdd:cd08940  158 HGVVGLTKVVA 168

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   1 MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQFEpQKTLFIQCDVADQQQLRDTFRKVVD 80
Cdd:PRK12825   2 GSLMGRVALVTGAARGLGRAIALRLARAGADVVVHYRSDEEAAEELVEAVEALG-RRAQAVQADVTDKAALEAAVAAAVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  81 HFGRLDILVNNAGVN--------NEKNWEKTLQINLVSVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYC 152
Cdd:PRK12825  81 RFGRIDILVNNAGIFedkpladmSDDEWDEVIDVNLSGVFHLLRAVVPPMRKQRGGR---IVNISSVAGLPGWPGRSNYA 157

                        170
                 ....*....|....
gi 224922801 153 ASKHGIVGFTRSAA 166
Cdd:PRK12825 158 AAKAGLVGLTKALA 171

17hydroxysteroid dehydrogenase type 10 (HSD10)-like, classical (c) SDRs; HSD10, also known as amyloid-peptide-binding alcohol dehydrogenase (ABAD), was previously identified as a L-3-hydroxyacyl-CoA dehydrogenase, HADH2. In fatty acid metabolism, HADH2 catalyzes the third step of beta-oxidation, the conversion of a hydroxyl to a keto group in the NAD-dependent oxidation of L-3-hydroxyacyl CoA. In addition to alcohol dehydrogenase and HADH2 activites, HSD10 has steroid dehydrogenase activity. Although the mechanism is unclear, HSD10 is implicated in the formation of amyloid beta-petide in the brain (which is linked to the development of Alzheimer's disease). Although HSD10 is normally concentrated in the mitochondria, in the presence of amyloid beta-peptide it translocates into the plasma membrane, where it's action may generate cytotoxic aldehydes and may lower estrogen levels through its use of 17-beta-estradiol as a substrate. HSD10 is a member of the SRD family, but differs from other SDRs by the presence of two insertions of unknown function. 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 224922801   4 NGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDeqfepqKTLFIQCDVADQQQLRDTFRKVVDHFG 83
Cdd:cd05371    1 KGLVAVVTGGASGLGLATVERLLAQGAKVVILDLPNSPGETVAKLGD------NCRFVPVDVTSEKDVKAALALAKAKFG 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  84 RLDILVNNAGV-------NNEKN-------WEKTLQINLVSVISGTYLGLDYMSKQ---NGGEGGIIINMSSLAGLMPVA 146
Cdd:cd05371   75 RLDIVVNCAGIavaaktyNKKGQqphslelFQRVINVNLIGTFNVIRLAAGAMGKNepdQGGERGVIINTASVAAFEGQI 154

                        170
                 ....*....|....*.
gi 224922801 147 QQPVYCASKHGIVGFT 162
Cdd:cd05371  155 GQAAYSASKGGIVGMT 170

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   1 MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQfePQKTLFIQCDVADQQQLRDTFRKVVD 80
Cdd:PRK06172   3 MTFSGKVALVTGGAAGIGRATALAFAREGAKVVVADRDAAGGEETVALIREA--GGEALFVACDVTRDAEVKALVEQTIA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  81 HFGRLDILVNNAGV---------NNEKNWEKTLQINLvsviSGTYLGLDY----MSKQNGGEggiIINMSSLAGLMPVAQ 147
Cdd:PRK06172  81 AYGRLDYAFNNAGIeieqgrlaeGSEAEFDAIMGVNV----KGVWLCMKYqiplMLAQGGGA---IVNTASVAGLGAAPK 153

                        170
                 ....*....|....*....
gi 224922801 148 QPVYCASKHGIVGFTRSAA 166
Cdd:PRK06172 154 MSIYAASKHAVIGLTKSAA 172

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801   4 NGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQfepqkTLFIQCDVADQQQLRDTFRKVVDHFG 83
Cdd:PRK08265   5 AGKVAIVTGGATLIGAAVARALVAAGARVAIVDIDADNGAAVAASLGER-----ARFIATDITDDAAIERAVATVVARFG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  84 RLDILVNNA------GVNNEKN-WEKTLQINLVSVISGTYLGLDYMSKQnggeGGIIINMSSLAGLMPVAQQPVYCASKH 156
Cdd:PRK08265  80 RVDILVNLActylddGLASSRAdWLAALDVNLVSAAMLAQAAHPHLARG----GGAIVNFTSISAKFAQTGRWLYPASKA 155

                        170
                 ....*....|
gi 224922801 157 GIVGFTRSAA 166
Cdd:PRK08265 156 AIRQLTRSMA 165

cyclohexanol reductases, including levodione reductase, classical (c) SDRs; Cyloclohexanol reductases,including (6R)-2,2,6-trimethyl-1,4-cyclohexanedione (levodione) reductase of Corynebacterium aquaticum, catalyze the reversible oxidoreduction of hydroxycyclohexanone derivatives. 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 224922801   6 KVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQFEPQKTLFIQCDVADQQQLRDTFRKVVDHFGRL 85
Cdd:cd05330    4 KVVLITGGGSGLGLATAVRLAKEGAKLSLVDLNEEGLEAAKAALLEIAPDAEVLLIKADVSDEAQVEAYVDATVEQFGRI 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224922801  86 DILVNNAGVNNEKN---------WEKTLQINLvsviSGTYLGLDYMSKQNGGEG-GIIINMSSLAGLMPVAQQPVYCASK 155
Cdd:cd05330   84 DGFFNNAGIEGKQNltedfgadeFDKVVSINL----RGVFYGLEKVLKVMREQGsGMIVNTASVGGIRGVGNQSGYAAAK 159

                        170
                 ....*....|.
gi 224922801 156 HGIVGFTRSAA 166
Cdd:cd05330  160 HGVVGLTRNSA 170