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 545478229  23 GMTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229     --------------------------------------------------------------------------------
Cdd:cd08936   81 avnlhggvdilvsnaavnpffgnildsteevwdkildvnvkatalmtkavvpemekrgggsvvivssvaafhpfpglgpy 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 103 ----------------------------------------LWMDKEKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASY 142
Cdd:cd08936  161 nvsktallgltknlapelaprnirvnclapgliktsfssaLWMDKAVEESMKETLRIRRLGQPEDCAGIVSFLCSEDASY 240

                        250
                 ....*....|....*.
gi 545478229 143 ITGETVVVGGGTPSRL 158
Cdd:cd08936  241 ITGETVVVGGGTPSRL 256

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 545478229  23 GMTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229     --------------------------------------------------------------------------------
Cdd:cd08936   81 avnlhggvdilvsnaavnpffgnildsteevwdkildvnvkatalmtkavvpemekrgggsvvivssvaafhpfpglgpy 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 103 ----------------------------------------LWMDKEKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASY 142
Cdd:cd08936  161 nvsktallgltknlapelaprnirvnclapgliktsfssaLWMDKAVEESMKETLRIRRLGQPEDCAGIVSFLCSEDASY 240

                        250
                 ....*....|....*.
gi 545478229 143 ITGETVVVGGGTPSRL 158
Cdd:cd08936  241 ITGETVVVGGGTPSRL 256

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGlSVTGTVCHVGKAEDRERLVAT------- 102
Cdd:PRK07231   3 LEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILAGG-RAIAVAADVSDEADVEAAVAAalerfgs 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 103 ---------------------------------------------LWMDK------------------------------ 107
Cdd:PRK07231  82 vdilvnnagtthrngplldvdeaefdrifavnvkspylwtqaavpAMRGEgggaivnvastaglrprpglgwynaskgav 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 108 ----------------------------------------EKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASYITGET 147
Cdd:PRK07231 162 itltkalaaelgpdkirvnavapvvvetglleafmgeptpENRAKFLATIPLGRLGTPEDIANAALFLASDEASWITGVT 241

                 ....*.
gi 545478229 148 VVVGGG 153
Cdd:PRK07231 242 LVVDGG 247

acetoin reductases; One member of this family, as characterized in Klebsiella terrigena, is described as able to interconvert acetoin + NADH with meso-2,3-butanediol + NAD(+). It is also called capable of irreversible reduction of diacetyl with NADH to acetoin. Blomqvist, et al. decline to specify either EC 1.1.1.4 which is (R,R)-butanediol dehydrogenase, or EC 1.1.1.5, which is acetoin dehydrogenase without a specified stereochemistry, for this enzyme. This enzyme is a homotetramer in the family of short chain dehydrogenases (pfam00106). Another member of this family, from Corynebacterium glutamicum, is called L-2,3-butanediol dehydrogenase (). [Energy metabolism, Fermentation]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229   72 AVATLQGEGLSVTGTVCHVGKAEDRERLVATLWMDKEKEESMK-----ETLRIRRLGEPEDCAGIVSFLCSEDASYITGE 146
Cdd:TIGR02415 164 AAQELAPKGITVNAYCPGIVKTPMWEEIDEETSEIAGKPIGEGfeefsSEIALGRPSEPEDVAGLVSFLASEDSDYITGQ 243

                  ....*..
gi 545478229  147 TVVVGGG 153
Cdd:TIGR02415 244 SILVDGG 250

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229  23 GMTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:cd08936    1 GVTRRDPLANKVALVTASTDGIGLAIARRLAQDGAHVVVSSRKQQNVDRAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229     --------------------------------------------------------------------------------
Cdd:cd08936   81 avnlhggvdilvsnaavnpffgnildsteevwdkildvnvkatalmtkavvpemekrgggsvvivssvaafhpfpglgpy 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 103 ----------------------------------------LWMDKEKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASY 142
Cdd:cd08936  161 nvsktallgltknlapelaprnirvnclapgliktsfssaLWMDKAVEESMKETLRIRRLGQPEDCAGIVSFLCSEDASY 240

                        250
                 ....*....|....*.
gi 545478229 143 ITGETVVVGGGTPSRL 158
Cdd:cd08936  241 ITGETVVVGGGTPSRL 256

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGlSVTGTVCHVGKAEDRERLVAT------- 102
Cdd:PRK07231   3 LEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILAGG-RAIAVAADVSDEADVEAAVAAalerfgs 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 103 ---------------------------------------------LWMDK------------------------------ 107
Cdd:PRK07231  82 vdilvnnagtthrngplldvdeaefdrifavnvkspylwtqaavpAMRGEgggaivnvastaglrprpglgwynaskgav 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 108 ----------------------------------------EKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASYITGET 147
Cdd:PRK07231 162 itltkalaaelgpdkirvnavapvvvetglleafmgeptpENRAKFLATIPLGRLGTPEDIANAALFLASDEASWITGVT 241

                 ....*.
gi 545478229 148 VVVGGG 153
Cdd:PRK07231 242 LVVDGG 247

SDR family oxidoreductase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVdQAVA-TLQGEGLSVTGTVCHVGKAEDRERLVATL 103
Cdd:PRK07035   6 LTGKIALVTGASRGIGEAIAKLLAQQGAHVIVSSRKLDGC-QAVAdAIVAAGGKAEALACHIGEMEQIDALFAHI 79

gluconate 5-dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATLwmdkEK 109
Cdd:PRK07097   8 LKGKIALITGASYGIGFAIAKAYAKAGATIVFNDINQELVDKGLAAYRELGIEAHGYVCDVTDEDGVQAMVSQI----EK 83

                 .
gi 545478229 110 E 110
Cdd:PRK07097  84 E 84

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR)-like, SDR; This subgroup resembles the SDR family, but does not have a perfect match to the NAD-binding motif or the catalytic tetrad characteristic of the SDRs. It includes the SDRs, Q9HYA2 from Pseudomonas aeruginosa PAO1 and APE0912 from Aeropyrum pernix K1. 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 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 545478229  32 NKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATLW 104
Cdd:cd05344    1 GKVALVTAASSGIGLAIARALAREGARVAICARNRENLERAASELRAGGAGVLAVVADLTDPEDIDRLVEKAG 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229   33 KVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQ 70

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 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGL-SVTGTVCHVGKAEDRERLVATLW---- 104
Cdd:cd05369    1 LKGKVAFITGGGTGIGKAIAKAFAELGASVAIAGRKPEVLEAAAEEISSATGgRAHPIQCDVRDPEAVEAAVDETLkefg 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229     --------------------------------------------------------------------------------
Cdd:cd05369   81 kidilinnaagnflapaeslspngfktvididlngtfnttkavgkrlieakhggsilnisatyaytgspfqvhsaaakag 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 105 --------------------------------MDK-----EKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASYITGET 147
Cdd:cd05369  161 vdaltrslavewgpygirvnaiapgpipttegMERlapsgKSEKKMIERVPLGRLGTPEEIANLALFLLSDAASYINGTT 240

                 ....*.
gi 545478229 148 VVVGGG 153
Cdd:cd05369  241 LVVDGG 246

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRE------------ 97
Cdd:cd05329    4 LEGKTALVTGGTKGIGYAIVEELAGLGAEVYTCARNQKELDECLTEWREKGFKVEGSVCDVSSRSERQelmdtvashfgg 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229     --------------------------------------------------------------------------------
Cdd:cd05329   84 klnilvnnagtnirkeakdyteedyslimstnfeaayhlsrlahpllkasgngnivfissvagviavpsgapygatkgal 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229  98 ----------------------------RLVATLWMDKEKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASYITGETVV 149
Cdd:cd05329  164 nqltrslacewakdnirvnavapwviatPLVEPVIQQKENLDKVIERTPLKRFGEPEEVAALVAFLCMPAASYITGQIIA 243

                 ....
gi 545478229 150 VGGG 153
Cdd:cd05329  244 VDGG 247

3-hydroxybutyrate dehydrogenase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVA 101
Cdd:PRK12429   2 LKGKVALVTGAASGIGLEIALALAKEGAKVVIADLNDEAAAAAAEALQKAGGKAIGVAMDVTDEEAINAGID 73

gluconate 5-dehydrogenase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:PRK08213  10 LSGKTALVTGGSRGLGLQIAEALGEAGARVVLSARKAEELEEAAAHLEALGIDALWIAADVADEADIERLAEE 82

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229  24 MTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATL 103
Cdd:PRK06124   3 ILQRFSLAGQVALVTGSARGLGFEIARALAGAGAHVLVNGRNAATLEAAVAALRAAGGAAEALAFDIADEEAVAAAFARI 82

SDR family oxidoreductase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 545478229  27 RDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATL 103
Cdd:PRK12826   1 TRDLEGRVALVTGAARGIGRAIAVRLAADGAEVIVVDICGDDAAATAELVEAAGGKARARQVDVRDRAALKAAVAAG 77

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229  22 SGMTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLqgEGLSVTGTVCHVGKAEDRERLVA 101
Cdd:PRK12829   1 SAIDLLKPLDGLRVLVTGGASGIGRAIAEAFAEAGARVHVCDVSEAALAATAARL--PGAKVTATVADVADPAQVERVFD 78

                 .
gi 545478229 102 T 102
Cdd:PRK12829  79 T 79

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGeglsVTGTVCHVGKAEDRERLVATL 103
Cdd:COG3967    3 LTGNTILITGGTSGIGLALAKRLHARGNTVIITGRREEKLEEAAAANPG----LHTIVLDVADPASIAALAEQV 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 545478229  31 ANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVtgtVCHVGKAEDRERLVATL 103
Cdd:COG4221    4 KGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAELGGRALAV---PLDVTDEAAVEAAVAAA 73

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
                 ....*....|....*....|....*....|....*....|....*....|..
gi 545478229  33 KVALVTASTDGIGFAIARRLAQDGA-HVVVSSRKQQNVDQAVATLQGEGLSV 83
Cdd:cd05324    1 KVALVTGANRGIGFEIVRQLAKSGPgTVILTARDVERGQAAVEKLRAEGLSV 52

short chain dehydrogenase; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTG 85
Cdd:PRK07576   7 FAGKNVVVVGGTSGINLGIAQAFARAGANVAVASRSQEKVDAAVAQLQQAGPEGLG 62

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVA 101
Cdd:PRK12939   5 LAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAAGGRAHAIAADLADPASVQRFFD 76

SDR family oxidoreductase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 545478229  25 TRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATL 103
Cdd:PRK07201 364 DLRGPLVGKVVLITGASSGIGRATAIKVAEAGATVFLVARNGEALDELVAEIRAKGGTAHAYTCDLTDSAAVDHTVKDI 442

SDR family oxidoreductase;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 545478229  96 RERLVATLWMDKEKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASYITGETVVVGGG 153
Cdd:PRK09242 194 RTPLTSGPLSDPDYYEQVIERTPMRRVGEPEEVAAAVAFLCMPAASYITGQCIAVDGG 251

short chain dehydrogenase; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 545478229 103 LWMDKEKEESMKETLRIRRLGEPEDCAGIVSFLCSEDASYITGETVVVGGG 153
Cdd:PRK07677 194 LWESEEAAKRTIQSVPLGRLGTPEEIAGLAYFLLSDEAAYINGTCITMDGG 244

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVATLWMD 106
Cdd:PRK08217   3 LKDKVIVITGGAQGLGRAMAEYLAQKGAKLALIDLNQEKLEEAVAECGALGTEVRGYAANVTDEEDVEATFAQIAED 79

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:PRK07478   4 LNGKVAIITGASSGIGRAAAKLFAREGAKVVVGARRQAELDQLVAEIRAEGGEAVALAGDVRDEAYAKALVAL 76

human Mgc4172-like, classical (c) SDRs; Human Mgc4172-like proteins, putative SDRs. These proteins are members of the SDR family, with a canonical active site tetrad and a typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEG 80
Cdd:cd05343    4 WRGRVALVTGASVGIGAAVARALVQHGMKVVGCARRVDKIEALAAECQSAG 54

SDR family oxidoreductase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 545478229  30 LANKVALVTASTD-GIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGE-GLS-VTGTVCHVGKAEDRERLVAT 102
Cdd:PRK07831  15 LAGKVVLVTAAAGtGIGSATARRALEEGARVVISDIHERRLGETADELAAElGLGrVEAVVCDVTSEAQVDALIDA 90

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 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQnvDQAVATLQ------GEGLSVTGTvchVGKAEDRERLVATl 103
Cdd:cd05358    1 LKGKVALVTGASSGIGKAIAIRLATAGANVVVNYRSKE--DAAEEVVEeikavgGKAIAVQAD---VSKEEDVVALFQS- 74

                 ....*
gi 545478229 104 wMDKE 108
Cdd:cd05358   75 -AIKE 78

Rhamnose utilisation protein RhaD, predicted bifunctional aldolase and dehydrogenase [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 545478229  24 MTRRDPLANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTV 87
Cdd:COG3347  417 MPKPKPLAGRVALVTGGAGGIGRATAARLAAEGAAVVVADLDGEAAEAAAAELGGGYGADAVDA 480

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 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVS-SRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLV-------- 100
Cdd:cd05362    1 LAGKVALVTGASRGIGRAIAKRLARDGASVVVNyASSKAAAEEVVAEIEAAGGKAIAVQADVSDPSQVARLFdaaekafg 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 101 ----------------------------------ATLWMDKEKEESMKETLRI--------------------------- 119
Cdd:cd05362   81 gvdilvnnagvmlkkpiaetseeefdrmftvntkGAFFVLQEAAKRLRDGGRIinisssltaaytpnygayagskaavea 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545478229 120 -----------------------------------------------RRLGEPEDCAGIVSFLCSEDASYITGETVVVGG 152
Cdd:cd05362  161 ftrvlakelggrgitvnavapgpvdtdmfyagkteeavegyakmsplGRLGEPEDIAPVVAFLASPDGRWVNGQVIRANG 240

                 .
gi 545478229 153 G 153
Cdd:cd05362  241 G 241

SDR family oxidoreductase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 545478229  36 LVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGlSVTGTVCHVGKAEDRERLVATLW 104
Cdd:PRK08340   4 LVTASSRGIGFNVARELLKKGARVVISSRNEENLEKALKELKEYG-EVYAVKADLSDKDDLKNLVKEAW 71

3-ketodihydrosphingosine reductase (KDSR) and related proteins, classical (c) SDR; These proteins include members identified as KDSR, ribitol type dehydrogenase, and others. The group shows strong conservation of the active site tetrad and glycine rich NAD-binding motif of the classical 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 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 545478229  33 KVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGE----GLSVTGTVCHVGKAEDRERLVATL 103
Cdd:cd08939    2 KHVLITGGSSGIGKALAKELVKEGANVIIVARSESKLEEAVEEIEAEanasGQKVSYISADLSDYEEVEQAFAQA 76

7 alpha-hydroxysteroid dehydrogenase (7 alpha-HSDH), classical (c) SDRs; This bacterial subgroup contains 7 alpha-HSDHs, including Escherichia coli 7 alpha-HSDH. 7 alpha-HSDH, a member of the SDR family, catalyzes the NAD+ -dependent dehydrogenation of a hydroxyl group at position 7 of the steroid skeleton of bile acids. In humans the two primary bile acids are cholic and chenodeoxycholic acids, these are formed from cholesterol in the liver. Escherichia coli 7 alpha-HSDH dehydroxylates these bile acids in the human intestine. Mammalian 7 alpha-HSDH activity has been found in livers. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 545478229  34 VALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLV 100
Cdd:cd05365    1 VAIVTGGAAGIGKAIAGTLAKAGASVVIADLKSEGAEAVAAAIQQAGGQAIGLECNVTSEQDLEAVV 67

7-alpha-hydroxysteroid dehydrogenase; Validated

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLV 100
Cdd:PRK06113   9 LDGKCAIITGAGAGIGKEIAITFATAGASVVVSDINADAANHVVDEIQQLGGQAFACRCDITSEQELSALA 79

SDR family oxidoreductase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 545478229  30 LANKVALVTASTDGIGFAIARRLAQDGAHVVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAT 102
Cdd:PRK07814   8 LDDQVAVVTGAGRGLGAAIALAFAEAGADVLIAARTESQLDEVAEQIRAAGRRAHVVAADLAHPEATAGLAGQ 80