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 110189609   1 AGLGGIGLDSSREDCQEGSqSLVILDRIDNPTAIAELKAINAKVTVTFYPYDVTMSVAETsKLLKTIFAKVNKVDLLING 80
Cdd:cd05323    7 GGASGIGLATAKLLLKKGA-KVAILDRNENPGAAAELQAINPKVKATFVQCDVTSWEQLA-AAFKKAIEKFGRVDILINN 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  81 AGILDDN----------QIERTIAVNFAGTVNTTTAIMEFWDKRKGGRGGVIANICSVTGFNAIHQVPVYSASKAAALSF 150
Cdd:cd05323   85 AGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGF 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609 151 TNSLAKLA-HITGVTAYSINPGITKTTLVRKFNSWLdveprvAELLLEHPTQTTQQCALNFVKAIEAN-KNGGIWMLDLG 228
Cdd:cd05323  165 TRSLADLLeYKTGVRVNAICPGFTNTPLLPDLVAKE------AEMLPSAPTQSPEVVAKAIVYLIEDDeKNGAIWIVDGG 238

                 ..
gi 110189609 229 RL 230
Cdd:cd05323  239 KL 240

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 110189609   1 AGLGGIGLDSSREDCQEGSqSLVILDRIDNPTAIAELKAINAKVTVTFYPYDVTMSVAETsKLLKTIFAKVNKVDLLING 80
Cdd:cd05323    7 GGASGIGLATAKLLLKKGA-KVAILDRNENPGAAAELQAINPKVKATFVQCDVTSWEQLA-AAFKKAIEKFGRVDILINN 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  81 AGILDDN----------QIERTIAVNFAGTVNTTTAIMEFWDKRKGGRGGVIANICSVTGFNAIHQVPVYSASKAAALSF 150
Cdd:cd05323   85 AGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGF 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609 151 TNSLAKLA-HITGVTAYSINPGITKTTLVRKFNSWLdveprvAELLLEHPTQTTQQCALNFVKAIEAN-KNGGIWMLDLG 228
Cdd:cd05323  165 TRSLADLLeYKTGVRVNAICPGFTNTPLLPDLVAKE------AEMLPSAPTQSPEVVAKAIVYLIEDDeKNGAIWIVDGG 238

                 ..
gi 110189609 229 RL 230
Cdd:cd05323  239 KL 240

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609   4 GGIGLDSSREDCQEGSQsLVILDRidNPTAIAELKA--INAKVTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGA 81
Cdd:COG0300   15 SGIGRALARALAARGAR-VVLVAR--DAERLEALAAelRAAGARVEVVALDVT-DPDAVAALAEAVLARFGPIDVLVNNA 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  82 GI--------LDDNQIERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGFNAIHQVPVYSASKAAALSFTNS 153
Cdd:COG0300   91 GVggggpfeeLDLEDLRRVFEVNVFGPVRLTRALLPLMRARGRGR---IVNVSSVAGLRGLPGMAAYAASKAALEGFSES 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609 154 LAKLAHITGVTAYSINPGITKTTLVRKfnswldveprvAELLLEHPTQTTQQCALNFVKAIEANKN------GGIWMLDL 227
Cdd:COG0300  168 LRAELAPTGVRVTAVCPGPVDTPFTAR-----------AGAPAGRPLLSPEEVARAILRALERGRAevyvgwDARLLARL 236

                 ....*
gi 110189609 228 GRLDP 232
Cdd:COG0300  237 LRLLP 241

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 110189609   1 AGLGGIGLDSSREDCQEGSqSLVILDRIDNPTAIAELKAINAKVTVTFYPYDVTMSVAETsKLLKTIFAKVNKVDLLING 80
Cdd:cd05323    7 GGASGIGLATAKLLLKKGA-KVAILDRNENPGAAAELQAINPKVKATFVQCDVTSWEQLA-AAFKKAIEKFGRVDILINN 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  81 AGILDDN----------QIERTIAVNFAGTVNTTTAIMEFWDKRKGGRGGVIANICSVTGFNAIHQVPVYSASKAAALSF 150
Cdd:cd05323   85 AGILDEKsylfagklppPWEKTIDVNLTGVINTTYLALHYMDKNKGGKGGVIVNIGSVAGLYPAPQFPVYSASKHGVVGF 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609 151 TNSLAKLA-HITGVTAYSINPGITKTTLVRKFNSWLdveprvAELLLEHPTQTTQQCALNFVKAIEAN-KNGGIWMLDLG 228
Cdd:cd05323  165 TRSLADLLeYKTGVRVNAICPGFTNTPLLPDLVAKE------AEMLPSAPTQSPEVVAKAIVYLIEDDeKNGAIWIVDGG 238

                 ..
gi 110189609 229 RL 230
Cdd:cd05323  239 KL 240

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 110189609   4 GGIGLDSSREDCQEGSqSLVILDRidNPTAIAELKAINAK-VTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGAG 82
Cdd:cd05233    8 SGIGRAIARRLAREGA-KVVLADR--NEEALAELAAIEALgGNAVAVQADVS-DEEDVEALVEEALEEFGRLDILVNNAG 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  83 I--------LDDNQIERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGFNAIHQVPVYSASKAAALSFTNSL 154
Cdd:cd05233   84 IarpgpleeLTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGGR---IVNISSVAGLRPLPGQAAYAASKAALEGLTRSL 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 110189609 155 AKLAHITGVTAYSINPGITKTTLVRKFNSWLDVEPRVAELLLEHPTQ 201
Cdd:cd05233  161 ALELAPYGIRVNAVAPGLVDTPMLAKLGPEEAEKELAAAIPLGRLGT 207

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 110189609   4 GGIGLDSSREDCQEGSQsLVILDRidNPTAIAELKA-INAK-VTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGA 81
Cdd:COG1028   16 SGIGRAIARALAAEGAR-VVITDR--DAEALEAAAAeLRAAgGRALAVAADVT-DEAAVEALVAAAVAAFGRLDILVNNA 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  82 GI--------LDDNQIERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGFNAIHQVPVYSASKAAALSFTNS 153
Cdd:COG1028   92 GItppgpleeLTEEDWDRVLDVNLKGPFLLTRAALPHMRERGGGR---IVNISSIAGLRGSPGQAAYAASKAAVVGLTRS 168

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 110189609 154 LAK-LAHiTGVTAYSINPGITKTTLVRKfnsWLDVEPRVAELLLEHP 199
Cdd:COG1028  169 LALeLAP-RGIRVNAVAPGPIDTPMTRA---LLGAEEVREALAARIP 211

human 17-beta-hydroxysteroid dehydrogenase XI-like, classical (c) SDRs; 17-beta-hydroxysteroid dehydrogenases (17betaHSD) are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 17betaHSD type XI, a classical SDR, preferentially converts 3alpha-Adiol to androsterone but not numerous other tested steroids. This subgroup of classical SDRs also includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. 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 110189609   2 GLGGIGldssREDCQEGSQ---SLVILDRidNPTAIAELKAINAKVTVTFYPYDVTMS----VAETSKLLKtifAKVNKV 74
Cdd:cd05339    7 GGSGIG----RLLALEFAKrgaKVVILDI--NEKGAEETANNVRKAGGKVHYYKCDVSkreeVYEAAKKIK---KEVGDV 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  75 DLLINGAGI--------LDDNQIERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGFNAIHQVPVYSASKAA 146
Cdd:cd05339   78 TILINNAGVvsgkklleLPDEEIEKTFEVNTLAHFWTTKAFLPDMLERNHGH---IVTIASVAGLISPAGLADYCASKAA 154

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 110189609 147 ALSFTNSLA---KLAHITGVTAYSINPGITKTTLVRkfnswlDVEPRVAELLlehPTQTTQQCALNFVKAIEANK 218
Cdd:cd05339  155 AVGFHESLRlelKAYGKPGIKTTLVCPYFINTGMFQ------GVKTPRPLLA---PILEPEYVAEKIVRAILTNQ 220

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 110189609   2 GLGGIGLDSSREDCQEGSQsLVILDRIDNPTAIAELKAINAKVTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGA 81
Cdd:cd05333    8 ASRGIGRAIALRLAAEGAK-VAVTDRSEEAAAETVEEIKALGGNAAALEADVS-DREAVEALVEKVEAEFGPVDILVNNA 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  82 GILDDN--------QIERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGF-NAIHQVPvYSASKAAALSFTN 152
Cdd:cd05333   86 GITRDNllmrmseeDWDAVINVNLTGVFNVTQAVIRAMIKRRSGR---IINISSVVGLiGNPGQAN-YAASKAGVIGFTK 161

                        170       180
                 ....*....|....*....|....*....
gi 110189609 153 SLAK-LAHiTGVTAYSINPGITKTTLVRK 180
Cdd:cd05333  162 SLAKeLAS-RGITVNAVAPGFIDTDMTDA 189

Porcine testicular carbonyl reductase (PTCR)-like, classical (c) SDRs; PTCR is a classical SDR which catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. Unlike most SDRs, PTCR functions as a monomer. This subgroup also includes human carbonyl reductase 1 (CBR1) and CBR3. CBR1 is an NADPH-dependent SDR with broad substrate specificity and may be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds. In addition it includes poppy NADPH-dependent salutaridine reductase which catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine, and Arabidopsis SDR1,a menthone reductase, which catalyzes the reduction of menthone to neomenthol, a compound with antimicrobial activity; SDR1 can also carry out neomenthol oxidation. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609   5 GIGLDSSREDCQEGSQSlVIL---DRIDNPTAIAELKaiNAKVTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGA 81
Cdd:cd05324   11 GIGFEIVRQLAKSGPGT-VILtarDVERGQAAVEKLR--AEGLSVRFHQLDVT-DDASIEAAADFVEEKYGGLDILVNNA 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  82 GIL---------DDNQIERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGfnaiHQVPVYSASKAAALSFTN 152
Cdd:cd05324   87 GIAfkgfddstpTREQARETMKTNFFGTVDVTQALLPLLKKSPAGR---IVNVSSGLG----SLTSAYGVSKAALNALTR 159

                        170       180
                 ....*....|....*....|...
gi 110189609 153 SLAKLAHITGVTAYSINPGITKT 175
Cdd:cd05324  160 ILAKELKETGIKVNACCPGWVKT 182

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609   2 GLGGIGLDSSREDCQEGSQsLVILDRIDNPTAIAELKAINAK-VTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLING 80
Cdd:PRK05557  13 ASRGIGRAIAERLAAQGAN-VVINYASSEAGAEALVAEIGALgGKALAVQGDVS-DAESVERAVDEAKAEFGGVDILVNN 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  81 AGILDDNQI--------ERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGF-NAIHQVPvYSASKAAALSFT 151
Cdd:PRK05557  91 AGITRDNLLmrmkeedwDRVIDTNLTGVFNLTKAVARPMMKQRSGR---IINISSVVGLmGNPGQAN-YAASKAGVIGFT 166

                        170       180       190
                 ....*....|....*....|....*....|.
gi 110189609 152 NSLAKLAHITGVTAYSINPGITKTTLVRKFN 182
Cdd:PRK05557 167 KSLARELASRGITVNAVAPGFIETDMTDALP 197

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 110189609   4 GGIGLDSSREDCQEGSQslVILDRIDNPTAIAELKAINA---KVTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLING 80
Cdd:cd08940   12 SGIGLGIARALAAAGAN--IVLNGFGDAAEIEAVRAGLAakhGVKVLYHGADLS-KPAAIEDMVAYAQRQFGGVDILVNN 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  81 AGI--------LDDNQIERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGFNAIHQVPVYSASKAAALSFTN 152
Cdd:cd08940   89 AGIqhvapiedFPTEKWDAIIALNLSAVFHTTRLALPHMKKQGWGR---IINIASVHGLVASANKSAYVAAKHGVVGLTK 165

                        170       180
                 ....*....|....*....|....*...
gi 110189609 153 SLAKLAHITGVTAYSINPGITKTTLVRK 180
Cdd:cd08940  166 VVALETAGTGVTCNAICPGWVLTPLVEK 193

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609   2 GLGGIGLDSSREDCQEGSQsLVILDRidNPTAIAELKAINAkvTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGA 81
Cdd:cd05370   13 GTSGIGLALARKFLEAGNT-VIITGR--REERLAEAKKELP--NIHTIVLDVG-DAESVEALAEALLSEYPNLDILINNA 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  82 GIL----------DDNQIERTIAVNFAGTVNTTTAIMEFWDKRKGGrggVIANICSVTGFNAIHQVPVYSASKAAALSFT 151
Cdd:cd05370   87 GIQrpidlrdpasDLDKADTEIDTNLIGPIRLIKAFLPHLKKQPEA---TIVNVSSGLAFVPMAANPVYCATKAALHSYT 163

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 110189609 152 NSLAKLAHITGVTAYSINPGITKTTLVRKFNSWLDVEPRvaelllehpTQTTQQCALNFVKAIEANK 218
Cdd:cd05370  164 LALRHQLKDTGVEVVEIVPPAVDTELHEERRNPDGGTPR---------KMPLDEFVDEVVAGLERGR 221

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 110189609   2 GLGGIGLDSSREDCQEGSQSLVI---LDRIDNPTAIAELKAINAKVTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLI 78
Cdd:cd08939    9 GSSGIGKALAKELVKEGANVIIVarsESKLEEAVEEIEAEANASGQKVSYISADLS-DYEEVEQAFAQAVEKGGPPDLVV 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  79 NGAGI--------LDDNQIERTIAVNFAGTVNTTTAIMEFWDKRKGGRggvIANICSVTGFNAIHQVPVYSASKAAALSF 150
Cdd:cd08939   88 NCAGIsipglfedLTAEEFERGMDVNYFGSLNVAHAVLPLMKEQRPGH---IVFVSSQAALVGIYGYSAYCPSKFALRGL 164

                 ....*
gi 110189609 151 TNSLA 155
Cdd:cd08939  165 AESLR 169

17hydroxysteroid dehydrogenase type 10 (HSD10)-like, classical (c) SDRs; HSD10, also known as amyloid-peptide-binding alcohol dehydrogenase (ABAD), was previously identified as a L-3-hydroxyacyl-CoA dehydrogenase, HADH2. In fatty acid metabolism, HADH2 catalyzes the third step of beta-oxidation, the conversion of a hydroxyl to a keto group in the NAD-dependent oxidation of L-3-hydroxyacyl CoA. In addition to alcohol dehydrogenase and HADH2 activites, HSD10 has steroid dehydrogenase activity. Although the mechanism is unclear, HSD10 is implicated in the formation of amyloid beta-petide in the brain (which is linked to the development of Alzheimer's disease). Although HSD10 is normally concentrated in the mitochondria, in the presence of amyloid beta-peptide it translocates into the plasma membrane, where it's action may generate cytotoxic aldehydes and may lower estrogen levels through its use of 17-beta-estradiol as a substrate. HSD10 is a member of the SRD family, but differs from other SDRs by the presence of two insertions of unknown function. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609   2 GLGGIGLDSSREDCQEGSQsLVILDRIDNPTAIAELKAINAKvtvtFYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGA 81
Cdd:cd05371   10 GASGLGLATVERLLAQGAK-VVILDLPNSPGETVAKLGDNCR----FVPVDVT-SEKDVKAALALAKAKFGRLDIVVNCA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  82 GI----------------LDDnqIERTIAVNFAGTVNTTTAIMEFWDKRK---GGRGGVIANICSVTGFNAIHQVPVYSA 142
Cdd:cd05371   84 GIavaaktynkkgqqphsLEL--FQRVINVNLIGTFNVIRLAAGAMGKNEpdqGGERGVIINTASVAAFEGQIGQAAYSA 161

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 110189609 143 SKAAALSFTNSLAK-LAHItGVTAYSINPGITKTTL 177
Cdd:cd05371  162 SKGGIVGMTLPIARdLAPQ-GIRVVTIAPGLFDTPL 196

carbonyl reductase sniffer-like, classical (c) SDRs; Sniffer is an NADPH-dependent carbonyl reductase of the classical SDR family. Studies in Drosophila melanogaster implicate Sniffer in the prevention of neurodegeneration due to aging and oxidative-stress. This subgroup also includes Rhodococcus sp. AD45 IsoH, which is an NAD-dependent 1-hydroxy-2-glutathionyl-2-methyl-3-butene dehydrogenase involved in isoprene metabolism, Aspergillus nidulans StcE encoded by a gene which is part of a proposed sterigmatocystin biosynthesis gene cluster, Bacillus circulans SANK 72073 BtrF encoded by a gene found in the butirosin biosynthesis gene cluster, and Aspergillus parasiticus nor-1 involved in the biosynthesis of aflatoxins. 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 110189609   5 GIGLDSSREDCQEGSQSLVILDRidNPTAIAELKAINAKVTVTFYPY-DVTMSVAETSKLLKTIFaKVNKVDLLINGAGI 83
Cdd:cd05325    9 GIGLELVRQLLARGNNTVIATCR--DPSAATELAALGASHSRLHILElDVTDEIAESAEAVAERL-GDAGLDVLINNAGI 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  84 LDDN---------QIERTIAVNFAGTVNTTTAimeFWDKRKGGRGGVIANICSVTG---FNAIHQVPVYSASKAAALSFT 151
Cdd:cd05325   86 LHSYgpasevdseDLLEVFQVNVLGPLLLTQA---FLPLLLKGARAKIINISSRVGsigDNTSGGWYSYRASKAALNMLT 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 110189609 152 NSLAKLAHITGVTAYSINPGITKTTLVRKF---NSWLDVEPRVAELL 195
Cdd:cd05325  163 KSLAVELKRDGITVVSLHPGWVRTDMGGPFaknKGPITPEESVAGLL 209

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609   2 GLGGIGLDSSREDCQEGSQsLVILDRiDNPTAIAELKAINAKV-----TVTFYPYDVTmSVAETSKLLKTIFAKVNKVDL 76
Cdd:PRK12827  14 GSGGLGRAIAVRLAADGAD-VIVLDI-HPMRGRAEADAVAAGIeaaggKALGLAFDVR-DFAATRAALDAGVEEFGRLDI 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  77 LINGAGILDD--------NQIERTIAVNFAGTVNTTTAIMEfwDKRKGGRGGVIANICSVTGFNAIH-QVPvYSASKAAA 147
Cdd:PRK12827  91 LVNNAGIATDaafaelsiEEWDDVIDVNLDGFFNVTQAALP--PMIRARRGGRIVNIASVAGVRGNRgQVN-YAASKAGL 167

                        170       180       190
                 ....*....|....*....|....*....|..
gi 110189609 148 LSFTNSLAKLAHITGVTAYSINPGITKTTLVR 179
Cdd:PRK12827 168 IGLTKTLANELAPRGITVNAVAPGAINTPMAD 199

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609   5 GIGLDSSREDCQEGSQsLVILDRidNPTAIAEL-KAINAKVTVTFYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGAGI 83
Cdd:PRK07231  16 GIGEGIARRFAAEGAR-VVVTDR--NEEAAERVaAEILAGGRAIAVAADVS-DEADVEAAVAAALERFGSVDILVNNAGT 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  84 ---------LDDNQIERTIAVNFAGTVNTTTAIMEFWdkrKGGRGGVIANICSVTGfnaIHQVP---VYSASKAAALSFT 151
Cdd:PRK07231  92 thrngplldVDEAEFDRIFAVNVKSPYLWTQAAVPAM---RGEGGGAIVNVASTAG---LRPRPglgWYNASKGAVITLT 165

                        170       180       190
                 ....*....|....*....|....*....|.
gi 110189609 152 NSLA-KLAHiTGVTAYSINPGITKTTLVRKF 181
Cdd:PRK07231 166 KALAaELGP-DKIRVNAVAPVVVETGLLEAF 195

classical (c) SDR, subgroup 6; These proteins are members of the classical SDR family, with a canonical active site tetrad and a fairly well conserved 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 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 110189609   5 GIGLDSSREDCQEGSQSLVILDRIDNPTAI-AELKAINAKVTVtfYPYDVTmSVAETSKLLKTIFAKVNKVDLLINGAGI 83
Cdd:cd05350    9 GIGRALAREFAKAGYNVALAARRTDRLDELkAELLNPNPSVEV--EILDVT-DEERNQLVIAELEAELGGLDLVIINAGV 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110189609  84 -----LDDNQIE---RTIAVNFAGTVNTTTAIMEFWDKRkgGRGGVIAnICSVTGFNAIHQVPVYSASKAAALSFTNSLA 155
Cdd:cd05350   86 gkgtsLGDLSFKafrETIDTNLLGAAAILEAALPQFRAK--GRGHLVL-ISSVAALRGLPGAAAYSASKAALSSLAESLR 162

                        170       180
                 ....*....|....*....|..
gi 110189609 156 KLAHITGVTAYSINPGITKTTL 177
Cdd:cd05350  163 YDVKKRGIRVTVINPGFIDTPL 184