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 1191833553  21 NLeVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMAANlMNSGVRLNAICPGF 100
Cdd:cd05323   110 NL-TGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGFTRSLADLLE-YKTGVRVNAICPGF 187

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1191833553 101 VNTPILKSIEKEEnmgqyieytdhiKDMMKYYGVLDPSMIANGLITLIEDDALNGAIMKITTSKGIHFQ 169
Cdd:cd05323   188 TNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIEDDEKNGAIWIVDGGKLIEIE 244

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  21 NLeVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMAANlMNSGVRLNAICPGF 100
Cdd:cd05323   110 NL-TGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGFTRSLADLLE-YKTGVRVNAICPGF 187

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1191833553 101 VNTPILKSIEKEEnmgqyieytdhiKDMMKYYGVLDPSMIANGLITLIEDDALNGAIMKITTSKGIHFQ 169
Cdd:cd05323   188 TNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIEDDEKNGAIWIVDGGKLIEIE 244

NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and metabolism]; NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family is part of the Pathway/BioSystem: Fatty acid biosynthesis

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  34 LDYMSKQnggEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSI-EKE 112
Cdd:COG1028   126 LPHMRER---GGGRIVNISSIAGLRGSPGQAAYAASKAAVVGLTRS--LALELAPRGIRVNAVAPGPIDTPMTRALlGAE 200

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1191833553 113 ENMGQYIEYTDhikdmMKYYGvlDPSMIANGLITLIEDDA--LNGAIMKI 160
Cdd:COG1028   201 EVREALAARIP-----LGRLG--TPEEVAAAVLFLASDAAsyITGQVLAV 243

pteridine reductase; Pteridine reductase is an enzyme used by trypanosomatids (including Trypanosoma cruzi and Leishmania major) to obtain reduced pteridines by salvage rather than biosynthetic pathways. Enzymes in T. cruzi described as pteridine reductase 1 (PTR1) and pteridine reductase 2 (PTR2) have different activity profiles. PTR1 is more active with with fully oxidized biopterin and folate than with reduced forms, while PTR2 reduces dihydrobiopterin and dihydrofolate but not oxidized pteridines. T. cruzi PTR1 and PTR2 are more similar to each other in sequence than either is to the pteridine reductase of Leishmania major, and all are included in this family.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1191833553  48 IINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMaaNLMNSGVRLNAICPGFVNTPILKSIEKEE 113
Cdd:TIGR02685 155 IVNLCDAMTDQPLLGFTMYTMAKHALEGLTRSAAL--ELAPLQIRVNGVAPGLSLLPDAMPFEVQE 218

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  21 NLeVSVISGTYLGLDYMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMAANlMNSGVRLNAICPGF 100
Cdd:cd05323   110 NL-TGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGFTRSLADLLE-YKTGVRVNAICPGF 187

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1191833553 101 VNTPILKSIEKEEnmgqyieytdhiKDMMKYYGVLDPSMIANGLITLIEDDALNGAIMKITTSKGIHFQ 169
Cdd:cd05323   188 TNTPLLPDLVAKE------------AEMLPSAPTQSPEVVAKAIVYLIEDDEKNGAIWIVDGGKLIEIE 244

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  21 NLeVSVISGTYLGLDYMSKQNGGeggIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGF 100
Cdd:cd05233   105 NL-TGVFLLTRAALPHMKKQGGG---RIVNISSVAGLRPLPGQAAYAASKAALEGLTRS--LALELAPYGIRVNAVAPGL 178

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1191833553 101 VNTPILKSIEKEENMGQYIEYTDHIKdmmkyygVLDPSMIANGLITLIEDDA--LNGAIMKIT 161
Cdd:cd05233   179 VDTPMLAKLGPEEAEKELAAAIPLGR-------LGTPEEVAEAVVFLASDEAsyITGQVIPVD 234

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  24 VSVISGTYLGLDYMSKQNGGeggIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNT 103
Cdd:COG0300   115 FGPVRLTRALLPLMRARGRG---RIVNVSSVAGLRGLPGMAAYAASKAALEGFSES--LRAELAPTGVRVTAVCPGPVDT 189

                  ..
gi 1191833553 104 PI 105
Cdd:COG0300   190 PF 191

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  25 SVISGTYLGLDYMskqngGEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTP 104
Cdd:pfam13561 107 SLFLLAKAALPLM-----KEGGSIVNLSSIGAERVVPNYNAYGAAKAALEALTRY--LAVELGPRGIRVNAISPGPIKTL 179

                          90
                  ....*....|....*.
gi 1191833553 105 ILKSIEKEENMGQYIE 120
Cdd:pfam13561 180 AASGIPGFDELLAAAE 195

3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  25 SVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAM--AAnlmnSGVRLNAICPGFVN 102
Cdd:PRK12429  115 GAFLTTKAALPIMKAQGGGR---IINMASVHGLVGSAGKAAYVSAKHGLIGLTKVVALegAT----HGVTVNAICPGYVD 187

                  ..
gi 1191833553 103 TP 104
Cdd:PRK12429  188 TP 189

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  25 SVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMAAnlMNSGVRLNAICPGFVNTP 104
Cdd:cd08940   115 AVFHTTRLALPHMKKQGWGR---IINIASVHGLVASANKSAYVAAKHGVVGLTKVVALET--AGTGVTCNAICPGWVLTP 189

                  ...
gi 1191833553 105 ILK 107
Cdd:cd08940   190 LVE 192

3beta17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; This subgroup includes members identified as 3beta17beta hydroxysteroid dehydrogenase, 20beta hydroxysteroid dehydrogenase, and R-alcohol dehydrogenase. These proteins exhibit the canonical active site tetrad and glycine rich NAD(P)-binding motif of the classical SDRs. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  21 NLEvSVISGTYLGLDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMAANLMNSGVRLNAICPGF 100
Cdd:cd05341   110 NLT-GVFLGTRAVIPPMKEAGGGS---IINMSSIEGLVGDPALAAYNASKGAVRGLTKSAALECATQGYGIRVNSVHPGY 185

                          90
                  ....*....|....*....
gi 1191833553 101 VNTPILKSI-EKEENMGQY 118
Cdd:cd05341   186 IYTPMTDELlIAQGEMGNY 204

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1191833553  34 LDYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSI 109
Cdd:PRK05557  126 ARPMMKQRSGR---IINISSVVGLMGNPGQANYAASKAGVIGFTKS--LARELASRGITVNAVAPGFIETDMTDAL 196

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 1191833553  35 DYMSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSIEKeen 114
Cdd:cd05333   121 RAMIKRRSGR---IINISSVVGLIGNPGQANYAASKAGVIGFTKS--LAKELASRGITVNAVAPGFIDTDMTDALPE--- 192

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1191833553 115 mgqyiEYTDHIKDM--MKYYGvlDPSMIANGLITLIEDDA 152
Cdd:cd05333   193 -----KVKEKILKQipLGRLG--TPEEVANAVAFLASDDA 225

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  24 VSVISGTYLGLDYMSKQNGGeggIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNT 103
Cdd:PRK07231  115 KSPYLWTQAAVPAMRGEGGG---AIVNVASTAGLRPRPGLGWYNASKGAVITLTKA--LAAELGPDKIRVNAVAPVVVET 189

                  ....*
gi 1191833553 104 PILKS 108
Cdd:PRK07231  190 GLLEA 194

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  34 LDYMSKQNGGeggIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRsaAMAANLMNSGVRLNAICPGFVNTPILKSIEKEE 113
Cdd:PRK05565  126 LPYMIKRKSG---VIVNISSIWGLIGASCEVLYSASKGAVNAFTK--ALAKELAPSGIRVNAVAPGAIDTEMWSSFSEED 200

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1191833553 114 NMGQYIEYTdhikdMMKyygVLDPSMIANGLITLIEDDA--LNGAIMKI 160
Cdd:PRK05565  201 KEGLAEEIP-----LGR---LGKPEEIAKVVLFLASDDAsyITGQIITV 241

L-iditol 2-dehydrogenase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191833553  43 GEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMAanLMNSGVRLNAICPGFVNTP 104
Cdd:PRK07067  130 GRGGKIINMASQAGRRGEALVSHYCATKAAVISYTQSAALA--LIRHGINVNAIAPGVVDTP 189

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  42 GGEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRsaAMAANLMNSGVRLNAICPGFVNTPilksiekeenMGQYIEY 121
Cdd:PRK12827  136 ARRGGRIVNIASVAGVRGNRGQVNYAASKAGLIGLTK--TLANELAPRGITVNAVAPGAINTP----------MADNAAP 203

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1191833553 122 TDHIKDMMKYYGVLDPSMIANGLITLIEDDA--LNGAIMKI 160
Cdd:PRK12827  204 TEHLLNPVPVQRLGEPDEVAALVAFLVSDAAsyVTGQVIPV 244

classical (c) SDR, subgroup 11; 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 1191833553  25 SVISGTYLGLDYMSKQNGGeggiIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMaaNLMNSGVRLNAICPGFVNTP 104
Cdd:cd05364   117 AVIYLTKLAVPHLIKTKGE----IVNVSSVAGGRSFPGVLYYCISKAALDQFTRCTAL--ELAPKGVRVNSVSPGVIVTG 190

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1191833553 105 ILKSIEKEENmgQYIEYTDHIKDMMKYYGVLDPSMIANGLITLIEDDA 152
Cdd:cd05364   191 FHRRMGMPEE--QYIKFLSRAKETHPLGRPGTVDEVAEAIAFLASDAS 236

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  27 ISGTYLGLDYMSKQNGGEG-GIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAAMAANlmNSGVRLNAICPGFVNTPI 105
Cdd:cd05330   115 LRGVFYGLEKVLKVMREQGsGMIVNTASVGGIRGVGNQSGYAAAKHGVVGLTRNSAVEYG--QYGIRINAIAPGAILTPM 192

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1191833553 106 ----LKSIEKE---ENMGQYIEYtdhikDMMKYYGvlDPSMIANGLITLIEDDA--LNGAIMKI 160
Cdd:cd05330   193 vegsLKQLGPEnpeEAGEEFVSV-----NPMKRFG--EPEEVAAVVAFLLSDDAgyVNAAVVPI 249

classical (c) SDR, subgroup 12; These are classical SDRs, with the canonical active site tetrad and glycine-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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553   3 SLNLRrlfssSAMWRTRHNLEVSVISGtylgldymskqnggeGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSAam 82
Cdd:cd08944   107 AINLR-----GTFLCCRHAAPRMIARG---------------GGSIVNLSSIAGQSGDPGYGAYGASKAAIRNLTRTL-- 164

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1191833553  83 AANLMNSGVRLNAICPGFVNTPILKS-IEKEENMGQYIEYTDHIKDMMKYYGVldPSMIANGLITLIEDDA 152
Cdd:cd08944   165 AAELRHAGIRCNALAPGLIDTPLLLAkLAGFEGALGPGGFHLLIHQLQGRLGR--PEDVAAAVVFLLSDDA 233

Polyketide ketoreductase, classical (c) SDR; Polyketide ketoreductase (KR) is a classical SDR with a characteristic NAD-binding pattern and active site tetrad. Aromatic polyketides include various aromatic compounds of pharmaceutical interest. Polyketide KR, part of the type II polyketide synthase (PKS) complex, is comprised of stand-alone domains that resemble the domains found in fatty acid synthase and multidomain type I PKS. 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 1191833553  41 NGGEG----GIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRsaAMAANLMNSGVRLNAICPGFVNTPILKSI 109
Cdd:cd08945   125 AGGMLergtGRIINIASTGGKQGVVHAAPYSASKHGVVGFTK--ALGLELARTGITVNAVCPGFVETPMAASV 195

SDR family oxidoreductase UcpA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  34 LDYMSKQNGGEggiIINMSSLAGLMpVAQ--QPVYCASKHGIIGFTRsaAMAANLMNSGVRLNAICPGFVNTPILKSIEK 111
Cdd:PRK08226  125 LPEMIARKDGR---IVMMSSVTGDM-VADpgETAYALTKAAIVGLTK--SLAVEYAQSGIRVNAICPGYVRTPMAESIAR 198

                  ...
gi 1191833553 112 EEN 114
Cdd:PRK08226  199 QSN 201

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1191833553  46 GIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTP 104
Cdd:PRK06550  120 GIIINMCSIASFVAGGGGAAYTASKHALAGFTKQ--LALDYAKDGIQVFGIAPGAVKTP 176

acetoacetyl-CoA reductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  25 SVISGTYLGLDYMSKqngGEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTP 104
Cdd:PRK12935  118 SVFNTTSAVLPYITE---AEEGRIISISSIIGQAGGFGQTNYSAAKAGMLGFTKS--LALELAKTNVTVNAICPGFIDTE 192

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1191833553 105 ILKSIekEENMGQYIEytdhIKDMMKYYGVLDPsmIANGLITLIEDDA 152
Cdd:PRK12935  193 MVAEV--PEEVRQKIV----AKIPKKRFGQADE--IAKGVVYLCRDGA 232

17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 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 1191833553  34 LDYMSKQnggEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSIEKEE 113
Cdd:cd05374   117 LPLMRKQ---GSGRIVNVSSVAGLVPTPFLGPYCASKAALEALSES--LRLELAPFGIKVTIIEPGPVRTGFADNAAGSA 191

                          90
                  ....*....|....*..
gi 1191833553 114 NMGQYIEYTDHIKDMMK 130
Cdd:cd05374   192 LEDPEISPYAPERKEIK 208

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  37 MSKQNGGEggiIINMSSLAGLMPVAQQPVYCASKHGIIGFTRsaAMAANLMNSGVRLNAICPGFVNTPILKSIEKEEnmg 116
Cdd:PRK12825  130 MRKQRGGR---IVNISSVAGLPGWPGRSNYAAAKAGLVGLTK--ALARELAEYGITVNMVAPGDIDTDMKEATIEEA--- 201

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1191833553 117 qyieyTDHIKDMMKYYGVLDPSMIANGLITLIEDDA--LNGAIMKIT 161
Cdd:PRK12825  202 -----REAKDAETPLGRSGTPEDIARAVAFLCSDASdyITGQVIEVT 243

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191833553  34 LDYMSKqnggeGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRSaaMAANLMNSGVRLNAICPGFVNTPILKSIEKEE 113
Cdd:PRK06701  168 LPHLKQ-----GSAIINTGSITGYEGNETLIDYSATKGAIHAFTRS--LAQSLVQKGIRVNAVAPGPIWTPLIPSDFDEE 240

                  ....*
gi 1191833553 114 NMGQY 118
Cdd:PRK06701  241 KVSQF 245

SDR family oxidoreductase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1191833553  45 GGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRsaAMAANLMNSGVRLNAICPGFVNTPI 105
Cdd:PRK07454  134 GGLIINVSSIAARNAFPQWGAYCVSKAALAAFTK--CLAEEERSHGIRVCTITLGAVNTPL 192

3-hydroxybutyrate dehydrogenase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1191833553  34 LDYMSKQNggEGGIIINMSSLAGLMPVAQQPVYCASKHGIIGFTRsaAMAANLMNSGVRLNAICPGFVNTPIL 106
Cdd:PRK13394  127 LKHMYKDD--RGGVVIYMGSVHSHEASPLKSAYVTAKHGLLGLAR--VLAKEGAKHNVRSHVVCPGFVRTPLV 195