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 767979563  23 GMTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767979563 103 AVKLHGGIDILVSNAAVNPFFGSIMDVTEEVWDKVI 138
Cdd:cd08936   81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDKIL 116

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  23 GMTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767979563 103 AVKLHGGIDILVSNAAVNPFFGSIMDVTEEVWDKVI 138
Cdd:cd08936   81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDKIL 116

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 767979563  28 DPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLH 107
Cdd:COG1028    2 TRLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGGRALAVAADVTDEAAVEALVAAAVAAF 81

                         90       100       110
                 ....*....|....*....|....*....|.
gi 767979563 108 GGIDILVSNAAVNPfFGSIMDVTEEVWDKVI 138
Cdd:COG1028   82 GRLDILVNNAGITP-PGPLEELTEEDWDRVL 111

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 767979563    33 KVALVTASTDGIGFAIARRLAQDGA-HVVVSSR---KQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHG 108
Cdd:smart00822   1 GTYLITGGLGGLGRALARWLAERGArRLVLLSRsgpDAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAAIPAVEG 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 767979563   109 GIDILVsNAAVNPFFGSIMDVTEEVWDKVI 138
Cdd:smart00822  81 PLTGVI-HAAGVLDDGVLASLTPERFAAVL 109

Porcine peroxisomal carbonyl reductase like, classical (c) SDR; This subgroup contains porcine peroxisomal carbonyl reductase and similar proteins. The porcine enzyme efficiently reduces retinals. This subgroup also includes human dehydrogenase/reductase (SDR family) member 4 (DHRS4), and human DHRS4L1. DHRS4 is a peroxisomal enzyme with 3beta-hydroxysteroid dehydrogenase activity; it catalyzes the reduction of 3-keto-C19/C21-steroids into 3beta-hydroxysteroids more efficiently than it does the retinal reduction. The human DHRS4 gene cluster contains DHRS4, DHRS4L2 and DHRS4L1. DHRS4L2 and DHRS4L1 are paralogs of DHRS4, DHRS4L2 being the most recent member. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  23 GMTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767979563 103 AVKLHGGIDILVSNAAVNPFFGSIMDVTEEVWDKVI 138
Cdd:cd08936   81 AVNLHGGVDILVSNAAVNPFFGNILDSTEEVWDKIL 116

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 767979563  28 DPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLH 107
Cdd:COG1028    2 TRLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGGRALAVAADVTDEAAVEALVAAAVAAF 81

                         90       100       110
                 ....*....|....*....|....*....|.
gi 767979563 108 GGIDILVSNAAVNPfFGSIMDVTEEVWDKVI 138
Cdd:COG1028   82 GRLDILVNNAGITP-PGPLEELTEEDWDRVL 111

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:PRK05653   3 LQGKTALVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRAAGGEARVLVFDVSDEAAVRALIEAAVEAFGA 82

                         90       100
                 ....*....|....*....|....*....
gi 767979563 110 IDILVSNAAVNPfFGSIMDVTEEVWDKVI 138
Cdd:PRK05653  83 LDILVNNAGITR-DALLPRMSEEDWDRVI 110

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVAT-LQGEGLSVTGTVCHVGKAEDRERLVATAVKLHG 108
Cdd:PRK05565   3 LMGKVAIVTGASGGIGRAIAELLAKEGAKVVIAYDINEEAAQELLEeIKEEGGDAIAVKADVSSEEDVENLVEQIVEKFG 82

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767979563 109 GIDILVSNAAVNpFFGSIMDVTEEVWDKVIYL 140
Cdd:PRK05565  83 KIDILVNNAGIS-NFGLVTDMTDEEWDRVIDV 113

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGlSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:PRK07326   4 LKGKVALITGGSKGIGFAIAEALLAEGYKVAITARDQKELEEAAAELNNKG-NVLGLAADVRDEADVQRAVDAIVAAFGG 82

                         90       100
                 ....*....|....*....|....*....
gi 767979563 110 IDILVSNAAVNpFFGSIMDVTEEVWDKVI 138
Cdd:PRK07326  83 LDVLIANAGVG-HFAPVEELTPEEWRLVI 110

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  27 RDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKL 106
Cdd:PRK12826   1 TRDLEGRVALVTGAARGIGRAIAVRLAADGAEVIVVDICGDDAAATAELVEAAGGKARARQVDVRDRAALKAAVAAGVED 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767979563 107 HGGIDILVSNAAVNPfFGSIMDVTEEVWDKVI 138
Cdd:PRK12826  81 FGRLDILVANAGIFP-LTPFAEMDDEQWERVI 111

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  22 SGMTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLqgEGLSVTGTVCHVGKAEDRERLVA 101
Cdd:PRK12829   1 SAIDLLKPLDGLRVLVTGGASGIGRAIAEAFAEAGARVHVCDVSEAALAATAARL--PGAKVTATVADVADPAQVERVFD 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 767979563 102 TAVKLHGGIDILVSNAAVNPFFGSIMDVTEEVWDKVI 138
Cdd:PRK12829  79 TAVERFGGLDVLVNNAGIAGPTGGIDEITPEQWEQTL 115

bifunctional aldolase/short-chain dehydrogenase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  24 MTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGlSVTGTVCHVGKAEDRERLVATA 103
Cdd:PRK08324 414 MPKPKPLAGKVALVTGAAGGIGKATAKRLAAEGACVVLADLDEEAAEAAAAELGGPD-RALGVACDVTDEAAVQAAFEEA 492

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767979563 104 VKLHGGIDILVSNAAVNPfFGSIMDVTEEVWDKV 137
Cdd:PRK08324 493 ALAFGGVDIVVSNAGIAI-SGPIEETSDEDWRRS 525

3-hydroxybutyrate dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:PRK12429   2 LKGKVALVTGAASGIGLEIALALAKEGAKVVIADLNDEAAAAAAEALQKAGGKAIGVAMDVTDEEAINAGIDYAVETFGG 81

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767979563 110 IDILVSNAA---VNPffgsIMDVTEEVWDKVIYLFL 142
Cdd:PRK12429  82 VDILVNNAGiqhVAP----IEDFPTEKWKKMIAIML 113

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 767979563  31 ANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVtgtVCHVGKAEDRERLVATAVKLHGGI 110
Cdd:COG4221    4 KGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAELGGRALAV---PLDVTDEAAVEAAVAAAVAEFGRL 80

                         90       100
                 ....*....|....*....|....*...
gi 767979563 111 DILVSNAAVNPfFGSIMDVTEEVWDKVI 138
Cdd:COG4221   81 DVLVNNAGVAL-LGPLEELDPEDWDRMI 107

Trans-2-enoyl-CoA reductase (TER) and 2,4-dienoyl-CoA reductase (DECR), atypical (a) SDR; TTER is a peroxisomal protein with a proposed role in fatty acid elongation. Fatty acid synthesis is known to occur in the both endoplasmic reticulum and mitochondria; peroxisomal TER has been proposed as an additional fatty acid elongation system, it reduces the double bond at C-2 as the last step of elongation. This system resembles the mitochondrial system in that acetyl-CoA is used as a carbon donor. TER may also function in phytol metabolism, reducting phytenoyl-CoA to phytanoyl-CoA in peroxisomes. DECR processes double bonds in fatty acids to increase their utility in fatty acid metabolism; it reduces 2,4-dienoyl-CoA to an enoyl-CoA. DECR is active in mitochondria and peroxisomes. This subgroup has the Gly-rich NAD-binding motif of the classical SDR family, but does not display strong identity to the canonical active site tetrad, and lacks the characteristic Tyr at the usual position. 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 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGL-SVTGTVCHVGKAEDRERLVATAVKLHG 108
Cdd:cd05369    1 LKGKVAFITGGGTGIGKAIAKAFAELGASVAIAGRKPEVLEAAAEEISSATGgRAHPIQCDVRDPEAVEAAVDETLKEFG 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 767979563 109 GIDILVSNAAVNpFFGSIMDVTEEVWDKVI 138
Cdd:cd05369   81 KIDILINNAAGN-FLAPAESLSPNGFKTVI 109

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:PRK12939   5 LAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAAGGRAHAIAADLADPASVQRFFDAAAAALGG 84

                         90       100
                 ....*....|....*....|....*....
gi 767979563 110 IDILVSNAAVNPfFGSIMDVTEEVWDKVI 138
Cdd:PRK12939  85 LDGLVNNAGITN-SKSATELDIDTWDAVM 112

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTD-GIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGE-GLS-VTGTVCHVGKAEDRERLVATAVKL 106
Cdd:PRK07831  15 LAGKVVLVTAAAGtGIGSATARRALEEGARVVISDIHERRLGETADELAAElGLGrVEAVVCDVTSEAQVDALIDAAVER 94

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767979563 107 HGGIDILVSNAAVNPfFGSIMDVTEEVWDKVI 138
Cdd:PRK07831  95 LGRLDVLVNNAGLGG-QTPVVDMTDDEWSRVL 125

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 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:cd05347    3 LKGKVALVTGASRGIGFGIASGLAEAGANIVINSRNEEKAEEAQQLIEKEGVEATAFTCDVSDEEAIKAAVEAIEEDFGK 82

                         90       100
                 ....*....|....*....|....*....
gi 767979563 110 IDILVSNAAVNPFFGSImDVTEEVWDKVI 138
Cdd:cd05347   83 IDILVNNAGIIRRHPAE-EFPEAEWRDVI 110

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 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQnvDQAVATLQ------GEGLSVTGTvchVGKAEDRERLVATA 103
Cdd:cd05358    1 LKGKVALVTGASSGIGKAIAIRLATAGANVVVNYRSKE--DAAEEVVEeikavgGKAIAVQAD---VSKEEDVVALFQSA 75

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 767979563 104 VKLHGGIDILVSNAAVNPFFGSImDVTEEVWDKVI 138
Cdd:cd05358   76 IKEFGTLDILVNNAGLQGDASSH-EMTLEDWNKVI 109

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 767979563  33 KVALVTASTDGIGFAIARRLAQDGA-HVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGGID 111
Cdd:cd05324    1 KVALVTGANRGIGFEIVRQLAKSGPgTVILTARDVERGQAAVEKLRAEGLSVRFHQLDVTDDASIEAAADFVEEKYGGLD 80

                         90       100
                 ....*....|....*....|....*..
gi 767979563 112 ILVSNAAVNPFFGSIMDVTEEVWDKVI 138
Cdd:cd05324   81 ILVNNAGIAFKGFDDSTPTREQARETM 107

tetrahydroxynaphthalene/trihydroxynaphthalene reductase-like, classical (c) SDRs; 1,3,6,8-tetrahydroxynaphthalene reductase (4HNR) of Magnaporthe grisea and the related 1,3,8-trihydroxynaphthalene reductase (3HNR) are typical members of the SDR family containing the canonical glycine rich NAD(P)-binding site and active site tetrad, and function in fungal melanin biosynthesis. This subgroup also includes an SDR from Norway spruce that may function to protect against both biotic and abitoic stress. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVS-SRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHG 108
Cdd:cd05362    1 LAGKVALVTGASRGIGRAIAKRLARDGASVVVNyASSKAAAEEVVAEIEAAGGKAIAVQADVSDPSQVARLFDAAEKAFG 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 767979563 109 GIDILVSNAAVNPfFGSIMDVTEEVWDKVI 138
Cdd:cd05362   81 GVDILVNNAGVML-KKPIAETSEEEFDRMF 109

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563   39 ASTDGIGFAIARRLAQDGAHVVVS--SRKQQNVDQAVATLQGEGLsvtgTVCHVGKAEDRERLVATAVKLHGGIDILVSN 116
Cdd:pfam13561   3 ANESGIGWAIARALAEEGAEVVLTdlNEALAKRVEELAEELGAAV----LPCDVTDEEQVEALVAAAVEKFGRLDILVNN 78

                          90       100
                  ....*....|....*....|...
gi 767979563  117 AAV-NPFFGSIMDVTEEVWDKVI 138
Cdd:pfam13561  79 AGFaPKLKGPFLDTSREDFDRAL 101

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:PRK07478   4 LNGKVAIITGASSGIGRAAAKLFAREGAKVVVGARRQAELDQLVAEIRAEGGEAVALAGDVRDEAYAKALVALAVERFGG 83

                         90       100
                 ....*....|....*....|....*....
gi 767979563 110 IDILVSNAAVNPFFGSIMDVTEEVWDKVI 138
Cdd:PRK07478  84 LDIAFNNAGTLGEMGPVAEMSLEGWRETL 112

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  32 NKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGGID 111
Cdd:PRK06181   1 GKVVIITGASEGIGRALAVRLARAGAQLVLAARNETRLASLAQELADHGGEALVVPTDVSDAEACERLIEAAVARFGGID 80

                 ....*...
gi 767979563 112 ILVSNAAV 119
Cdd:PRK06181  81 ILVNNAGI 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  33 KVALVTASTDGIGFAIARRLAQDGAHVVVSS-RKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGGID 111
Cdd:PRK12745   3 PVALVTGGRRGIGLGIARALAAAGFDLAINDrPDDEELAATQQELRALGVEVIFFPADVADLSAHEAMLDAAQAAWGRID 82

                         90       100
                 ....*....|....*....|....*...
gi 767979563 112 ILVSNAAVNPFF-GSIMDVTEEVWDKVI 138
Cdd:PRK12745  83 CLVNNAGVGVKVrGDLLDLTPESFDRVL 110

(S)-acetoin forming diacetyl reductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  32 NKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGGID 111
Cdd:PRK08643   2 SKVALVTGAGQGIGFAIAKRLVEDGFKVAIVDYNEETAQAAADKLSKDGGKAIAVKADVSDRDQVFAAVRQVVDTFGDLN 81

                         90       100
                 ....*....|....*....|....*.
gi 767979563 112 ILVSNAAVNPfFGSIMDVTEEVWDKV 137
Cdd:PRK08643  82 VVVNNAGVAP-TTPIETITEEQFDKV 106

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQ--GEGLSVTGTVCHVGKAEDRERLVATAVKLH 107
Cdd:PRK07063   5 LAGKVALVTGAAQGIGAAIARAFAREGAAVALADLDAALAERAAAAIArdVAGARVLAVPADVTDAASVAAAVAAAEEAF 84

                         90       100
                 ....*....|....*....|....*....
gi 767979563 108 GGIDILVSNAAVNpFFGSIMDVTEEVWDK 136
Cdd:PRK07063  85 GPLDVLVNNAGIN-VFADPLAMTDEDWRR 112

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVAtlqgEGLSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:cd05370    3 LTGNTVLITGGTSGIGLALARKFLEAGNTVIITGRREERLAEAKK----ELPNIHTIVLDVGDAESVEALAEALLSEYPN 78

                         90
                 ....*....|
gi 767979563 110 IDILVSNAAV 119
Cdd:cd05370   79 LDILINNAGI 88

gluconate 5-dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:PRK08085   7 LAGKNILITGSAQGIGFLLATGLAEYGAEIIINDITAERAELAVAKLRQEGIKAHAAPFNVTHKQEVEAAIEHIEKDIGP 86

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767979563 110 IDILVSNAAV---NPFfgsiMDVTEEVWDKVI 138
Cdd:PRK08085  87 IDVLINNAGIqrrHPF----TEFPEQEWNDVI 114

L-iditol 2-dehydrogenase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979563  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRkqqNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATAVKLHGG 109
Cdd:PRK07067   4 LQGKVALLTGAASGIGEAVAERYLAEGARVVIADI---KPARARLAALEIGPAAIAVSLDVTRQDSIDRIVAAAVERFGG 80