dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an NAD-binding protein related to the SDRs. It converts dihydrobiopterin into tetrahydrobiopterin, a cofactor necessary in catecholamines synthesis. Dihydropteridine reductase has the YXXXK of these tyrosine-dependent oxidoreductases, but lacks the typical upstream Asn and Ser catalytic residues. 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 17647337   3 AGRVVIYGGKGALGSACVDHFKANNYWVGSIDLTENEKADVSIVVPRDASWVEQEETVVSKVGESlaGEKLDAVICVAGG 82
Cdd:cd05334   1 ARVVLVYGGRGALGSAVVQAFKSRGWWVASIDLAENEEADASIIVLDSDSFTEQAKQVVASVARL--SGKVDALICVAGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  83 WAGGNAK-KDLAKNADLMWKQSVLTSAISAAVAAQHLKAGGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTRSLGAEKS 161
Cdd:cd05334  79 WAGGSAKsKSFVKNWDLMWKQNLWTSFIASHLATKHLLSGGLLVLTGAKAALEPTPGMIGYGAAKAAVHQLTQSLAAENS 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17647337 162 GLPAGSLAVSILPVTLDTPMNRKWMPDADFGTWTPLTEVAGLFLKWTQDQERPKTGSLLQLIT 224
Cdd:cd05334 159 GLPAGSTANAILPVTLDTPANRKAMPDADFSSWTPLEFIAELILFWASGAARPKSGSLIPVVT 221

dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an NAD-binding protein related to the SDRs. It converts dihydrobiopterin into tetrahydrobiopterin, a cofactor necessary in catecholamines synthesis. Dihydropteridine reductase has the YXXXK of these tyrosine-dependent oxidoreductases, but lacks the typical upstream Asn and Ser catalytic residues. 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 17647337   3 AGRVVIYGGKGALGSACVDHFKANNYWVGSIDLTENEKADVSIVVPRDASWVEQEETVVSKVGESlaGEKLDAVICVAGG 82
Cdd:cd05334   1 ARVVLVYGGRGALGSAVVQAFKSRGWWVASIDLAENEEADASIIVLDSDSFTEQAKQVVASVARL--SGKVDALICVAGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  83 WAGGNAK-KDLAKNADLMWKQSVLTSAISAAVAAQHLKAGGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTRSLGAEKS 161
Cdd:cd05334  79 WAGGSAKsKSFVKNWDLMWKQNLWTSFIASHLATKHLLSGGLLVLTGAKAALEPTPGMIGYGAAKAAVHQLTQSLAAENS 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17647337 162 GLPAGSLAVSILPVTLDTPMNRKWMPDADFGTWTPLTEVAGLFLKWTQDQERPKTGSLLQLIT 224
Cdd:cd05334 159 GLPAGSTANAILPVTLDTPANRKAMPDADFSSWTPLEFIAELILFWASGAARPKSGSLIPVVT 221

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337     6 VVIYGGKGALGSACVDHFKANNYWVGSIDLTEN----------EKADVSIVVPRDASWVEQEETVVSKVGESLAgeKLDA 75
Cdd:pfam00106   3 ALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEkleavakelgALGGKALFIQGDVTDRAQVKALVEQAVERLG--RLDI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337    76 VICVAGGWAGGNAKKDLAKNadlmWKQSV---LTSAISAAVAA-QHLKAG--GLLALTGAKPALEGTPGMIGYGMAKAAV 149
Cdd:pfam00106  81 LVNNAGITGLGPFSELSDED----WERVIdvnLTGVFNLTRAVlPAMIKGsgGRIVNISSVAGLVPYPGGSAYSASKAAV 156

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 17647337   150 HQLTRSLGAEksGLPAGSLAVSILPVTLDTPMNRKWMPD 188
Cdd:pfam00106 157 IGFTRSLALE--LAPHGIRVNAVAPGGVDTDMTKELRED 193

dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an NAD-binding protein related to the SDRs. It converts dihydrobiopterin into tetrahydrobiopterin, a cofactor necessary in catecholamines synthesis. Dihydropteridine reductase has the YXXXK of these tyrosine-dependent oxidoreductases, but lacks the typical upstream Asn and Ser catalytic residues. 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 17647337   3 AGRVVIYGGKGALGSACVDHFKANNYWVGSIDLTENEKADVSIVVPRDASWVEQEETVVSKVGESlaGEKLDAVICVAGG 82
Cdd:cd05334   1 ARVVLVYGGRGALGSAVVQAFKSRGWWVASIDLAENEEADASIIVLDSDSFTEQAKQVVASVARL--SGKVDALICVAGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  83 WAGGNAK-KDLAKNADLMWKQSVLTSAISAAVAAQHLKAGGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTRSLGAEKS 161
Cdd:cd05334  79 WAGGSAKsKSFVKNWDLMWKQNLWTSFIASHLATKHLLSGGLLVLTGAKAALEPTPGMIGYGAAKAAVHQLTQSLAAENS 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17647337 162 GLPAGSLAVSILPVTLDTPMNRKWMPDADFGTWTPLTEVAGLFLKWTQDQERPKTGSLLQLIT 224
Cdd:cd05334 159 GLPAGSTANAILPVTLDTPANRKAMPDADFSSWTPLEFIAELILFWASGAARPKSGSLIPVVT 221

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 17647337   6 VVIYGGKGALGSACVDHFKANNYWVGSIDLTENEKADVS---------IVVPRDASWVEQEETVVSKVGEslAGEKLDAV 76
Cdd:cd05233   1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAaiealggnaVAVQADVSDEEDVEALVEEALE--EFGRLDIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  77 ICVAGGWAGGNAKKDLAKNADLMWKQSVLTSAISAAVAAQHLKA--GGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTR 154
Cdd:cd05233  79 VNNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKqgGGRIVNISSVAGLRPLPGQAAYAASKAALEGLTR 158

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17647337 155 SLGAEksGLPAGSLAVSILPVTLDTPMNRKWMPDADFGTWTPLT---------EVAGLFLKWTQDQERPKTGSLLQL 222
Cdd:cd05233 159 SLALE--LAPYGIRVNAVAPGLVDTPMLAKLGPEEAEKELAAAIplgrlgtpeEVAEAVVFLASDEASYITGQVIPV 233

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 17647337 114 AAQHLKA--GGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTRSLGAEksGLPAGSLAVSILPVTLDTPMNRKWMPDADF 191
Cdd:COG1028 125 ALPHMRErgGGRIVNISSIAGLRGSPGQAAYAASKAAVVGLTRSLALE--LAPRGIRVNAVAPGPIDTPMTRALLGAEEV 202

2,3 dihydro-2,3 dihydrozybenzoate dehydrogenases, classical (c) SDRs; 2,3 dihydro-2,3 dihydrozybenzoate dehydrogenase shares the characteristics of the classical SDRs. This subgroup includes Escherichai coli EntA which catalyzes the NAD+-dependent oxidation of 2,3-dihydro-2,3-dihydroxybenzoate to 2,3-dihydroxybenzoate during biosynthesis of the siderophore Enterobactin. 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 17647337   6 VVIYGGKGALGSACVDHFKANNYWVGSIDLTENEKADVSIVV------PRDASWVEQeetVVSKVGEslAGEKLDAVICV 79
Cdd:cd05331   1 VIVTGAAQGIGRAVARHLLQAGATVIALDLPFVLLLEYGDPLrltpldVADAAAVRE---VCSRLLA--EHGPIDALVNC 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  80 AGGWAGGNAKKDLAKNadlmWKQSVLTSAISAAVA----AQHLKA--GGLLALTGAKPAleGTP--GMIGYGMAKAAVHQ 151
Cdd:cd05331  76 AGVLRPGATDPLSTED----WEQTFAVNVTGVFNLlqavAPHMKDrrTGAIVTVASNAA--HVPriSMAAYGASKAALAS 149

                       170       180       190
                ....*....|....*....|....*....|..
gi 17647337 152 LTRSLGAEKSglPAGSLAVSILPVTLDTPMNR 183
Cdd:cd05331 150 LSKCLGLELA--PYGVRCNVVSPGSTDTAMQR 179

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  111 AAVAAQHLKAGGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTRSLGaeKSGLPAGSLAVSILPVTLDTPMNRKWMPD-- 188
Cdd:PRK06701 164 TKAALPHLKQGSAIINTGSITGYEGNETLIDYSATKGAIHAFTRSLA--QSLVQKGIRVNAVAPGPIWTPLIPSDFDEek 241

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 17647337  189 -ADFGTWTPL------TEVAGLFLKWTQDQERPKTGSLLQLITTNGIT 229
Cdd:PRK06701 242 vSQFGSNTPMqrpgqpEELAPAYVFLASPDSSYITGQMLHVNGGVIVN 289

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 17647337  61 VSKVGESLAGEKLDAVICVAG-GWAGGNAKKDLAKNADLMWKqsvlTSAISAAVAAQHL------KAGGLLALTGAKPA- 132
Cdd:cd05325  64 AEAVAERLGDAGLDVLINNAGiLHSYGPASEVDSEDLLEVFQ----VNVLGPLLLTQAFlplllkGARAKIINISSRVGs 139

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17647337 133 LEGTP--GMIGYGMAKAAVHQLTRSLGAEKSglPAGSLAVSILPVTLDTPMNRKwmPDADFGTWTPLTEVAGLF 204
Cdd:cd05325 140 IGDNTsgGWYSYRASKAALNMLTKSLAVELK--RDGITVVSLHPGWVRTDMGGP--FAKNKGPITPEESVAGLL 209

NADP-dependent 3-hydroxy acid dehydrogenase YdfG [Energy production and conversion]; NADP-dependent 3-hydroxy acid dehydrogenase YdfG is part of the Pathway/BioSystem: Pyrimidine degradation

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  72 KLDAVICVAGGWAGGNAKKDLAKNADLMWKQSVLTSAISAAVAAQHLKA--GGLLALTGAKPALEGTPGMIGYGMAKAAV 149
Cdd:COG4221  79 RLDVLVNNAGVALLGPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRArgSGHIVNISSIAGLRPYPGGAVYAATKAAV 158

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 17647337 150 HQLTRSLGAEksGLPAGSLAVSILPVTLDTPMNRKWMPDAD 190
Cdd:COG4221 159 RGLSESLRAE--LRPTGIRVTVIEPGAVDTEFLDSVFDGDA 197

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 17647337   6 VVIYGGKGALGSACVDHFKANNYWVGSIDLTENEKA---------DVSIV-VPRDASWVEQEETVVSKVGESLAgeKLDa 75
Cdd:cd05323   3 AIITGGASGIGLATAKLLLKKGAKVAILDRNENPGAaaelqainpKVKATfVQCDVTSWEQLAAAFKKAIEKFG--RVD- 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  76 vICVAGgwAGGNAKKDLAKNADLM--WKQSV---LTSAISAAVAAQHL------KAGGLLALTGAKPALEGTPGMIGYGM 144
Cdd:cd05323  80 -ILINN--AGILDEKSYLFAGKLPppWEKTIdvnLTGVINTTYLALHYmdknkgGKGGVIVNIGSVAGLYPAPQFPVYSA 156

                       170
                ....*....|...
gi 17647337 145 AKAAVHQLTRSLG 157
Cdd:cd05323 157 SKHGVVGFTRSLA 169

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 17647337 108 AISAAVAAQHLKAGGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTRSLGAE--KSGLPAGSLAvsilPVTLDTPMNRKW 185
Cdd:cd08944 116 CCRHAAPRMIARGGGSIVNLSSIAGQSGDPGYGAYGASKAAIRNLTRTLAAElrHAGIRCNALA----PGLIDTPLLLAK 191

                ....*
gi 17647337 186 MPDAD 190
Cdd:cd08944 192 LAGFE 196

Tthb094 and related proteins, classical (c) SDRs; Tthb094 from Thermus Thermophilus is a classical SDR which binds NADP. Members of this subgroup contain the YXXXK active site characteristic of SDRs. Also, an upstream Asn residue of the canonical catalytic tetrad is partially conserved in this subgroup of proteins of undetermined 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 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 17647337   6 VVIYGGKGALGSACVDHFKANNYWVGSIdlTENEKADVSIVVPRDASWVEQEETVVSKVgESLAGE--KLDAVICVAGGW 83
Cdd:cd11730   1 ALILGATGGIGRALARALAGRGWRLLLS--GRDAGALAGLAAEVGALARPADVAAELEV-WALAQElgPLDLLVYAAGAI 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  84 AGgnakKDLAKNADLMWKQSVLTSAISAAVAAQH----LKAGGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTRSLGAE 159
Cdd:cd11730  78 LG----KPLARTKPAAWRRILDANLTGAALVLKHalalLAAGARLVFLGAYPELVMLPGLSAYAAAKAALEAYVEVARKE 153

                       170       180
                ....*....|....*....|..
gi 17647337 160 KSGLPagslAVSILPVTLDTPM 181
Cdd:cd11730 154 VRGLR----LTLVRPPAVDTGL 171

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337    5 RVVIYGGKGALGSACVDHFKANNYWVGSIDLTENE-----------------KADVSIVVPRDASWVEQE-ETVVSKVGe 66
Cdd:PRK12827   8 RVLITGGSGGLGRAIAVRLAADGADVIVLDIHPMRgraeadavaagieaaggKALGLAFDVRDFAATRAAlDAGVEEFG- 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337   67 slageKLDAVICVAGGwaggNAKKDLAKNADLMWKQSVLTSAISAAVAAQHL-------KAGGLLALTGAKPALEGTPGM 139
Cdd:PRK12827  87 -----RLDILVNNAGI----ATDAAFAELSIEEWDDVIDVNLDGFFNVTQAAlppmiraRRGGRIVNIASVAGVRGNRGQ 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  140 IGYGMAKAAVHQLTRSLGAEKSglPAGSLAVSILPVTLDTPMNRKWMPD------ADFGTWTPLTEVAGLFLKWTQDQER 213
Cdd:PRK12827 158 VNYAASKAGLIGLTKTLANELA--PRGITVNAVAPGAINTPMADNAAPTehllnpVPVQRLGEPDEVAALVAFLVSDAAS 235

                        250
                 ....*....|....
gi 17647337  214 PKTGsllQLITTNG 227
Cdd:PRK12827 236 YVTG---QVIPVDG 246

Lin1944 and related proteins, classical (c) SDRs; Lin1944 protein from Listeria Innocua is a classical SDR, it contains a glycine-rich motif similar to the canonical motif of the SDR NAD(P)-binding site. However, the typical SDR active site residues are absent in this subgroup of proteins of undetermined 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 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 17647337   6 VVIYGGKGALGSACVDHFKannywvgsidlteNEKADVSIV------VPRDASWVEQEETVVSKVGeslageKLDAVICV 79
Cdd:cd11731   1 IIVIGATGTIGLAVAQLLS-------------AHGHEVITAgrssgdYQVDITDEASIKALFEKVG------HFDAIVST 61

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  80 AGGWAGGNAKKDLAKNADLMWKQSVLTSAISAAVAAQHLKAGGLLALTGAKPALEGTPGMIGYGMAKAAVHQLTRSLGAE 159
Cdd:cd11731  62 AGDAEFAPLAELTDADFQRGLNSKLLGQINLVRHGLPYLNDGGSITLTSGILAQRPIPGGAAAATVNGALEGFVRAAAIE 141

                       170       180
                ....*....|....*....|....*...
gi 17647337 160 ksgLPAGS--LAVSilPVTLDTPMNRKW 185
Cdd:cd11731 142 ---LPRGIriNAVS--PGVVEESLEAYG 164

human dehydrogenase/reductase (SDR family) member 1 (DHRS1) and human hydroxysteroid dehydrogenase-like protein 2 (HSDL2), classical (c) SDRs; This subgroup includes human DHRS1 and human HSDL2 and related proteins. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. DHRS1 mRNA has been detected in many tissues, liver, heart, skeletal muscle, kidney and pancreas; a longer transcript is predominantly expressed in the liver , a shorter one in the heart. HSDL2 may play a part in fatty acid metabolism, as it is found in peroxisomes. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337  93 AKNADLMWKQSVLTSAISAAVAAQHL-KAGGLLALTGAKP-ALEGTPGMIGYGMAKAAVHQLTRSLGAEKSGlpaGSLAV 170
Cdd:cd05338 113 AKRFDLMQRVNLRGTYLLSQAALPHMvKAGQGHILNISPPlSLRPARGDVAYAAGKAGMSRLTLGLAAELRR---HGIAV 189

                        90       100       110
                ....*....|....*....|....*....|...
gi 17647337 171 SIL-PVTL-DTPMNRKWMPDADFGTWTPLTEVA 201
Cdd:cd05338 190 NSLwPSTAiETPAATELSGGSDPARARSPEILS 222

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337    3 AGRVVIYGGKGA-LGSACVDHFKANNYWVGSIDLTENEKADVS---------IVVPRDASWVEQEETVVSKVgeSLAGEK 72
Cdd:PRK06138   4 AGRVAIVTGAGSgIGRATAKLFAREGARVVVADRDAEAAERVAaaiaaggraFARQGDVGSAEAVEALVDFV--AARWGR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647337   73 LDAVICVAGGWAGGNAKKDLAKNADLMWKQSVLTSAISAAVAAQHLK--AGGLLALTGAKPALEGTPGMIGYGMAKAAVH 150
Cdd:PRK06138  82 LDVLVNNAGFGCGGTVVTTDEADWDAVMRVNVGGVFLWAKYAIPIMQrqGGGSIVNTASQLALAGGRGRAAYVASKGAIA 161

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 17647337  151 QLTRSLGAE--KSGLPAGSLAvsilPVTLDTPMNRK 184
Cdd:PRK06138 162 SLTRAMALDhaTDGIRVNAVA----PGTIDTPYFRR 193