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 308044580   8 LAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKLLGTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVEK 87
Cdd:cd09762    1 LAGKTLFITGASRGIGKAIALKAARDGANVVIAAKTAEPHPKLPGTIYTAAEEIEAAGGKALPCIVDIRDEDQVRAAVEK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  88 AIKKFG-------------------------------------------------------------------------A 94
Cdd:cd09762   81 AVEKFGgidilvnnasaisltgtldtpmkrydlmmgvntrgtylcskaclpylkksknphilnlspplnlnpkwfknhtA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  95 YTIAKYGMSMYVLGMAEEFK-GEIAVNALWPKTAIHTAAMDMLGGPGIESQCRKVDIIADAAYSIFQKPKS-FTGNFVID 172
Cdd:cd09762  161 YTMAKYGMSMCVLGMAEEFKpGGIAVNALWPRTAIATAAMNMLGGVDVAACCRKPEIMADAAYAILTKPSSeFTGNFLID 240

                 ...
gi 308044580 173 ENI 175
Cdd:cd09762  241 EEV 243

human hydroxysteroid dehydrogenase-like protein 2 (HSDL2), classical (c) SDRs; This subgroup includes human HSDL2 and related protens. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. HSDL2 may play a part in fatty acid metabolism, as it is found in peroxisomes. 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 308044580   8 LAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKLLGTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVEK 87
Cdd:cd09762    1 LAGKTLFITGASRGIGKAIALKAARDGANVVIAAKTAEPHPKLPGTIYTAAEEIEAAGGKALPCIVDIRDEDQVRAAVEK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  88 AIKKFG-------------------------------------------------------------------------A 94
Cdd:cd09762   81 AVEKFGgidilvnnasaisltgtldtpmkrydlmmgvntrgtylcskaclpylkksknphilnlspplnlnpkwfknhtA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  95 YTIAKYGMSMYVLGMAEEFK-GEIAVNALWPKTAIHTAAMDMLGGPGIESQCRKVDIIADAAYSIFQKPKS-FTGNFVID 172
Cdd:cd09762  161 YTMAKYGMSMCVLGMAEEFKpGGIAVNALWPRTAIATAAMNMLGGVDVAACCRKPEIMADAAYAILTKPSSeFTGNFLID 240

                 ...
gi 308044580 173 ENI 175
Cdd:cd09762  241 EEV 243

Putative sterol carrier protein, contains SCP2 domain [Lipid transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580 238 EETFRIVKDSLSD-DVVKATQAIYLFELSGEDGGTWFLDLKsKGGNVGYGEPSDQADVVMSMTTDDFVKMFSGKLKPTMA 316
Cdd:COG3255    1 DEWAEALCEKLNAaDAAAGWDGVVQFVITGEGGGAYYLVID-DGKCTVSEGDDDDADVTLTASYEDWKKLLTGELDPMTA 79

                         90       100
                 ....*....|....*....|....*
gi 308044580 317 FMSGKLKIKGNMALAIKLEKLMNQM 341
Cdd:COG3255   80 FMTGKLKVEGDMGLAMKLMSLFKAL 104

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 308044580   7 RLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAqphpkllGTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVE 86
Cdd:COG1028    3 RLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDA-------EALEAAAAELRAAGGRALAVAADVTDEAAVEALVA 75

                 ....*..
gi 308044580  87 KAIKKFG 93
Cdd:COG1028   76 AAVAAFG 82

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 308044580   15 ITGASRGIGKAIALKAAKDGANIVI----AAKTAQPHPklLGTiytaAEEIEAV----GGKALPCIVDVRDEQQISAAVE 86
Cdd:TIGR04504   6 VTGAARGIGAATVRRLAADGWRVVAvdlcADDPAVGYP--LAT----RAELDAVaaacPDQVLPVIADVRDPAALAAAVA 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 308044580   87 KAIKKFGAYTIAKYGMSMYVLGM------AEEFKGEIAVNA--LWpKTAiHTAAMDMLGGPGiESQCRKVDIIADAA 155
Cdd:TIGR04504  80 LAVERWGRLDAAVAAAGVIAGGRplwettDAELDLLLDVNLrgVW-NLA-RAAVPAMLARPD-PRGGRFVAVASAAA 153

human hydroxysteroid dehydrogenase-like protein 2 (HSDL2), classical (c) SDRs; This subgroup includes human HSDL2 and related protens. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. HSDL2 may play a part in fatty acid metabolism, as it is found in peroxisomes. 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 308044580   8 LAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKLLGTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVEK 87
Cdd:cd09762    1 LAGKTLFITGASRGIGKAIALKAARDGANVVIAAKTAEPHPKLPGTIYTAAEEIEAAGGKALPCIVDIRDEDQVRAAVEK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  88 AIKKFG-------------------------------------------------------------------------A 94
Cdd:cd09762   81 AVEKFGgidilvnnasaisltgtldtpmkrydlmmgvntrgtylcskaclpylkksknphilnlspplnlnpkwfknhtA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  95 YTIAKYGMSMYVLGMAEEFK-GEIAVNALWPKTAIHTAAMDMLGGPGIESQCRKVDIIADAAYSIFQKPKS-FTGNFVID 172
Cdd:cd09762  161 YTMAKYGMSMCVLGMAEEFKpGGIAVNALWPRTAIATAAMNMLGGVDVAACCRKPEIMADAAYAILTKPSSeFTGNFLID 240

                 ...
gi 308044580 173 ENI 175
Cdd:cd09762  241 EEV 243

human dehydrogenase/reductase (SDR family) member 1 (DHRS1) and human hydroxysteroid dehydrogenase-like protein 2 (HSDL2), classical (c) SDRs; This subgroup includes human DHRS1 and human HSDL2 and related proteins. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. DHRS1 mRNA has been detected in many tissues, liver, heart, skeletal muscle, kidney and pancreas; a longer transcript is predominantly expressed in the liver , a shorter one in the heart. HSDL2 may play a part in fatty acid metabolism, as it is found in peroxisomes. 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 308044580   8 LAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQ-----PHPKLLGTIYTAAEEIEAVGGKALPCIVDVRDEQQIS 82
Cdd:cd05338    1 LSGKVAFVTGASRGIGRAIALRLAKAGATVVVAAKTASegdngSAKSLPGTIEETAEEIEAAGGQALPIVVDVRDEDQVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  83 AAVEKAIKKFG--------------------------------------------------------------------- 93
Cdd:cd05338   81 ALVEATVDQFGrldilvnnagaiwlslvedtpakrfdlmqrvnlrgtyllsqaalphmvkagqghilnispplslrparg 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  94 --AYTIAKYGMSMYVLGMAEEFKG-EIAVNALWPKTAIHTAAMDMLGGPGIESQCRKVDIIADAAYSIFQKPK-SFTGNF 169
Cdd:cd05338  161 dvAYAAGKAGMSRLTLGLAAELRRhGIAVNSLWPSTAIETPAATELSGGSDPARARSPEILSDAVLAILSRPAaERTGLV 240

                 ....*.
gi 308044580 170 VIDENI 175
Cdd:cd05338  241 VIDEEL 246

SCP-2 sterol transfer family; This domain is involved in binding sterols. It is found in the SCP2 protein as well as the C terminus of the enzyme estradiol 17 beta-dehydrogenase EC:1.1.1.62. The UNC-24 protein contains an SPFH domain pfam01145.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  245 KDSLSDDVVKATQA-IYLFELSGEdGGTWFLDLKSKGGNVGyGEPSDQADVVMSMTTDDFVKMFSGKLKPTMAFMSGKLK 323
Cdd:pfam02036   7 RDPAARELLKKLNGkVIRFDLTDL-GLSLTLDLKDGGGRVL-AGDEGKADVTLSASDSDLLALATGKLNPQKAFMQGKLK 84

                          90
                  ....*....|....*
gi 308044580  324 IKGNMALAIKLEKLM 338
Cdd:pfam02036  85 IEGDMELAQKLEGLL 99

3-oxoacyl-ACP reductase FabG;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   7 RLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQphpkllgTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVE 86
Cdd:PRK05653   2 SLQGKTALVTGASRGIGRAIALRLAADGAKVVIYDSNEE-------AAEALAAELRAAGGEARVLVFDVSDEAAVRALIE 74

                         90
                 ....*....|.
gi 308044580  87 KAIKKFGAYTI 97
Cdd:PRK05653  75 AAVEAFGALDI 85

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   8 LAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKllgtiyTAAEEIEAVGGKALPCIVDVRDEQQISAAVEK 87
Cdd:PRK05557   3 LEGKVALVTGASRGIGRAIAERLAAQGANVVINYASSEAGAE------ALVAEIGALGGKALAVQGDVSDAESVERAVDE 76

                 ....*.
gi 308044580  88 AIKKFG 93
Cdd:PRK05557  77 AKAEFG 82

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  12 TVFITGASRGIGKAIALKAAKDGANIVIAAKTAqphpkllGTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVEKAIKK 91
Cdd:PRK07109  10 VVVITGASAGVGRATARAFARRGAKVVLLARGE-------EGLEALAAEIRAAGGEALAVVADVADAEAVQAAADRAEEE 82

                 ..
gi 308044580  92 FG 93
Cdd:PRK07109  83 LG 84

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   7 RLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKLlgtiytaAEEIEAVGGKALPCIVDVRDEQQISAAVE 86
Cdd:COG0300    2 SLTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEAL-------AAELRAAGARVEVVALDVTDPDAVAALAE 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 308044580  87 KAIKKFGAYTI----AKYGMSMYVLGM-AEEFKGEIAVNAL 122
Cdd:COG0300   75 AVLARFGPIDVlvnnAGVGGGGPFEELdLEDLRRVFEVNVF 115

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 308044580  13 VFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHpkllgtiyTAAEEIEAVGGKALPCIVDVRDEQQISAAVEKAIKKF 92
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEAL--------AELAAIEALGGNAVAVQADVSDEEDVEALVEEALEEF 72

                 .
gi 308044580  93 G 93
Cdd:cd05233   73 G 73

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  12 TVFITGASRGIGKAIALKAAKDGANIVIAAKTAQphpkllgTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVEKAIKK 91
Cdd:PRK07677   3 VVIITGGSSGMGKAMAKRFAEEGANVVITGRTKE-------KLEEAKLEIEQFPGQVLTVQMDVRNPEDVQKMVEQIDEK 75

                 ..
gi 308044580  92 FG 93
Cdd:PRK07677  76 FG 77

3-hydroxybutyrate dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   7 RLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKllgtiytAAEEIEAVGGKALPCIVDVRDEQQISAAVE 86
Cdd:PRK12429   1 MLKGKVALVTGAASGIGLEIALALAKEGAKVVIADLNDEAAAA-------AAEALQKAGGKAIGVAMDVTDEEAINAGID 73

                 ....*..
gi 308044580  87 KAIKKFG 93
Cdd:PRK12429  74 YAVETFG 80

beta-Keto acyl carrier protein reductase (BKR), involved in Type II FAS, classical (c) SDRs; This subgroup includes the Escherichai coli K12 BKR, FabG. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet) NAD(P)(H) binding region and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H) binding pattern: TGxxxGxG in classical SDRs. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P) binding motif and an altered active site motif (YXXXN). Fungal type type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P) binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr-151 and Lys-155, and well as Asn-111 (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  12 TVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPkllgtiyTAAEEIEAVGGKALPCIVDVRDEQQISAAVEKAIKK 91
Cdd:cd05333    2 VALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAA-------ETVEEIKALGGNAAALEADVSDREAVEALVEKVEAE 74

                 ....*.
gi 308044580  92 FGAYTI 97
Cdd:cd05333   75 FGPVDI 80

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  12 TVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPhpkllgTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVEKAIKK 91
Cdd:cd05366    4 VAIITGAAQGIGRAIAERLAADGFNIVLADLNLEE------AAKSTIQEISEAGYNAVAVGADVTDKDDVEALIDQAVEK 77

                 ..
gi 308044580  92 FG 93
Cdd:cd05366   78 FG 79

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   7 RLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKLlgtiytaAEEIEAVGGKALPCIVDVRDEQQISAAVE 86
Cdd:PRK07478   3 RLNGKVAIITGASSGIGRAAAKLFAREGAKVVVGARRQAELDQL-------VAEIRAEGGEAVALAGDVRDEAYAKALVA 75

                         90
                 ....*....|..
gi 308044580  87 KAIKKFGAYTIA 98
Cdd:PRK07478  76 LAVERFGGLDIA 87

(S)-acetoin forming diacetyl reductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  14 FITGASRGIGKAIALKAAKDGANIVIA---AKTAQphpkllgtiyTAAEEIEAVGGKALPCIVDVRDEQQISAAVEKAIK 90
Cdd:PRK08643   6 LVTGAGQGIGFAIAKRLVEDGFKVAIVdynEETAQ----------AAADKLSKDGGKAIAVKADVSDRDQVFAAVRQVVD 75

                 ...
gi 308044580  91 KFG 93
Cdd:PRK08643  76 TFG 78

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  10 GCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQphpKLLGTIYtAAEEIEAVGGKALPCI-VDVRDEQQISAAVEKA 88
Cdd:cd08939    1 GKHVLITGGSSGIGKALAKELVKEGANVIIVARSES---KLEEAVE-EIEAEANASGQKVSYIsADLSDYEEVEQAFAQA 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 308044580  89 IKKFGA----YTIAKYGMSMYVLGM-AEEFKGEIAVNALWPKTAIHTAAMDMLGGPG-----IESQCRKVDIIADAAYS 157
Cdd:cd08939   77 VEKGGPpdlvVNCAGISIPGLFEDLtAEEFERGMDVNYFGSLNVAHAVLPLMKEQRPghivfVSSQAALVGIYGYSAYC 155

human dehydrogenase/reductase (SDR family) member 1 (DHRS1) -like, classical (c) SDRs; This subgroup includes human DHRS1 and related proteins. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. DHRS1 mRNA has been detected in many tissues, liver, heart, skeletal muscle, kidney and pancreas; a longer transcript is predominantly expressed in the liver , a shorter one in the heart. 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 308044580   8 LAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQphPKLLGTIytaaEEIEAVGGKALPCIVDVRDEQQISAAVEK 87
Cdd:cd09763    1 LSGKIALVTGASRGIGRGIALQLGEAGATVYITGRTIL--PQLPGTA----EEIEARGGKCIPVRCDHSDDDEVEALFER 74

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   7 RLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQphpkllgTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVE 86
Cdd:PRK07814   7 RLDDQVAVVTGAGRGLGAAIALAFAEAGADVLIAARTES-------QLDEVAEQIRAAGRRAHVVAADLAHPEATAGLAG 79

                 ....*..
gi 308044580  87 KAIKKFG 93
Cdd:PRK07814  80 QAVEAFG 86

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   4 NTGRLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKLlgtiytaAEEIEAVGGKALPCIVDVRDEQQISA 83
Cdd:PRK12939   1 MASNLAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEAREL-------AAALEAAGGRAHAIAADLADPASVQR 73

                         90
                 ....*....|.
gi 308044580  84 AVEKAIKKFGA 94
Cdd:PRK12939  74 FFDAAAAALGG 84

7-alpha-hydroxysteroid dehydrogenase; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   3 PNTGRLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQphpkllgTIYTAAEEIEAVGGKALPCIVDVRDEQQIS 82
Cdd:PRK06113   4 SDNLRLDGKCAIITGAGAGIGKEIAITFATAGASVVVSDINAD-------AANHVVDEIQQLGGQAFACRCDITSEQELS 76

                         90
                 ....*....|....*
gi 308044580  83 AAVEKAIKKFGAYTI 97
Cdd:PRK06113  77 ALADFALSKLGKVDI 91

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 308044580   8 LAGCTVFITGASRGIGKAIALKAAKDGANIVI----AAKTAQphpkllgtiyTAAEEIEAVGGKALPCIVDVRDEQQISA 83
Cdd:cd05362    1 LAGKVALVTGASRGIGRAIAKRLARDGASVVVnyasSKAAAE----------EVVAEIEAAGGKAIAVQADVSDPSQVAR 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580  84 AVEKAIKKFGAYTIAKYGMSMYVLG-----MAEEFKGEIAVNALWPKTAIHTAAMDMLGGPGIESQCRKVDIIADAAYSI 158
Cdd:cd05362   71 LFDAAEKAFGGVDILVNNAGVMLKKpiaetSEEEFDRMFTVNTKGAFFVLQEAAKRLRDGGRIINISSSLTAAYTPNYGA 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580 159 FQKPKS----FTGNFVIDeniLKEEGIEnfdVYAIKPGhPLQPDFFLD-EYPEAVSKKVESTgavpefkeeklqlqPKPR 233
Cdd:cd05362  151 YAGSKAaveaFTRVLAKE---LGGRGIT---VNAVAPG-PVDTDMFYAgKTEEAVEGYAKMS--------------PLGR 209

                        250
                 ....*....|....*...
gi 308044580 234 SGAVEETFRIVKDSLSDD 251
Cdd:cd05362  210 LGEPEDIAPVVAFLASPD 227

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   5 TGRLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKllgtiytAAEEIEAV--GGKALPCIVDVRDEQQIS 82
Cdd:PRK07063   2 MNRLAGKVALVTGAAQGIGAAIARAFAREGAAVALADLDAALAER-------AAAAIARDvaGARVLAVPADVTDAASVA 74

                         90
                 ....*....|..
gi 308044580  83 AAVEKAIKKFGA 94
Cdd:PRK07063  75 AAVAAAEEAFGP 86

bifunctional aldolase/short-chain dehydrogenase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308044580   3 PNTGRLAGCTVFITGASRGIGKAIALKAAKDGANIVIA---AKTAQphpkllgtiyTAAEEIEAvGGKALPCIVDVRDEQ 79
Cdd:PRK08324 415 PKPKPLAGKVALVTGAAGGIGKATAKRLAAEGACVVLAdldEEAAE----------AAAAELGG-PDRALGVACDVTDEA 483

                         90
                 ....*....|....
gi 308044580  80 QISAAVEKAIKKFG 93
Cdd:PRK08324 484 AVQAAFEEAALAFG 497

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 308044580   8 LAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQphpkllgTIYTAAEEIEAVGGKALPCIVDVRDEQQISAAVEK 87
Cdd:cd05347    3 LKGKVALVTGASRGIGFGIASGLAEAGANIVINSRNEE-------KAEEAQQLIEKEGVEATAFTCDVSDEEAIKAAVEA 75

                 ....*.
gi 308044580  88 AIKKFG 93
Cdd:cd05347   76 IEEDFG 81