Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGnlkeKDILVLPLDLTDTGSHEAATKAVLQ 127
Cdd:COG0300     3 LTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAG----ARVEVVALDVTDPDAVAALAEAVLA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547 128 EFGR---------------------------------------------------------------------------- 131
Cdd:COG0300    79 RFGPidvlvnnagvggggpfeeldledlrrvfevnvfgpvrltrallplmrargrgrivnvssvaglrglpgmaayaask 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547 132 ----GFFNGLRTELATYpGIIVSNICPGPVQSNIVENSlagevtktigNNGDQSHKMTTSRCVRLMLISMANDLKEVWIS 207
Cdd:COG0300   159 aaleGFSESLRAELAPT-GVRVTAVCPGPVDTPFTARA----------GAPAGRPLLSPEEVARAILRALERGRAEVYVG 227

                         250       260
                  ....*....|....*....|....*
gi 1016149547 208 eQPFLLVTYLWQYMPTWAWWITNKM 232
Cdd:COG0300   228 -WDARLLARLLRLLPRLFDRLLRRA 251

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGnlkeKDILVLPLDLTDTGSHEAATKAVLQEFGR 131
Cdd:pfam00106   2 VALVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALG----GKALFIQGDVTDRAQVKALVEQAVERLGR 77

sepiapterin reductase; This model describes sepiapterin reductase, a member of the short chain dehydrogenase/reductase family. The enzyme catalyzes the last step in the biosynthesis of tetrahydrobiopterin. A similar enzyme in Bacillus cereus was isolated for its ability to convert benzil to (S)-benzoin, a property sepiapterin reductase also shares. Cutoff scores for this model are set such that benzil reductase scores between trusted and noise cutoffs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1016149547  55 VTGASSGIGEELAYQLSKL----GVSLVLSARRVHELERVKRRCLENGNlkEKDILVLPLDLTDTGSHEAATKAVLQ 127
Cdd:TIGR01500   5 VTGASRGFGRTIAQELAKClkspGSVLVLSARNDEALRQLKAEIGAERS--GLRVVRVSLDLGAEAGLEQLLKALRE 79

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGnlkeKDILVLPLDLTDTGSHEAATKAVLQ 127
Cdd:COG0300     3 LTGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAG----ARVEVVALDVTDPDAVAALAEAVLA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547 128 EFGR---------------------------------------------------------------------------- 131
Cdd:COG0300    79 RFGPidvlvnnagvggggpfeeldledlrrvfevnvfgpvrltrallplmrargrgrivnvssvaglrglpgmaayaask 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547 132 ----GFFNGLRTELATYpGIIVSNICPGPVQSNIVENSlagevtktigNNGDQSHKMTTSRCVRLMLISMANDLKEVWIS 207
Cdd:COG0300   159 aaleGFSESLRAELAPT-GVRVTAVCPGPVDTPFTARA----------GAPAGRPLLSPEEVARAILRALERGRAEVYVG 227

                         250       260
                  ....*....|....*....|....*
gi 1016149547 208 eQPFLLVTYLWQYMPTWAWWITNKM 232
Cdd:COG0300   228 -WDARLLARLLRLLPRLFDRLLRRA 251

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 1016149547  49 TDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENgnlkekdILVLPLDLTDTGSHEAATKAVLQE 128
Cdd:COG4221     4 KGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAELGGR-------ALAVPLDVTDEAAVEAAVAAAVAE 76

                  ...
gi 1016149547 129 FGR 131
Cdd:COG4221    77 FGR 79

17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELErvkrrclENGNLKEKDILVLPLDLTDTGSHEAATKAVLQEFGR 131
Cdd:cd05374     2 VVLITGCSSGIGLALALALAAQGYRVIATARNPDKLE-------SLGELLNDNLEVLELDVTDEESIKAAVKEVIERFGR 74

classical (c) SDR, subgroup 11; SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGnLKEKDILVLPLDLTDTGSHEAATKAVLQ 127
Cdd:cd05364     1 LSGKVAIITGSSSGIGAGTAILFARLGARLALTGRDAERLEETRQSCLQAG-VSEKKILLVVADLTEEEGQDRIISTTLA 79

                  ....
gi 1016149547 128 EFGR 131
Cdd:cd05364    80 KFGR 83

short chain dehydrogenase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELErvkrrclengNLKEKDILVLPLDLTDTGSHEAATKAVLQEFGR 131
Cdd:PRK06182    5 VALVTGASSGIGKATARRLAAQGYTVYGAARRVDKME----------DLASLGVHPLSLDVTDEASIKAAVDTIIAEEGR 74

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1016149547  53 VWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNlkekdILVLPLDLTDTGSHEAATKAVLQEFGR 131
Cdd:cd05233     1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELAAIEALGGN-----AVAVQADVSDEEDVEALVEEALEEFGR 74

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  42 RRPEWELTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNlkekDILVLPLDLTDTGSHEAA 121
Cdd:PRK07201  363 RDLRGPLVGKVVLITGASSGIGRATAIKVAEAGATVFLVARNGEALDELVAEIRAKGG----TAHAYTCDLTDSAAVDHT 438

                          90
                  ....*....|
gi 1016149547 122 TKAVLQEFGR 131
Cdd:PRK07201  439 VKDILAEHGH 448

classical (c) SDR, subgroup 5; These proteins are members of the classical SDR family, with a canonical active site tetrad and a typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  51 MVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRClenGNLKEKDILVLPLDLTDTGSHEAATKAVLQEFG 130
Cdd:cd05346     1 KTVLITGASSGIGEATARRFAKAGAKLILTGRRAERLQELADEL---GAKFPVKVLPLQLDVSDRESIEAALENLPEEFR 77

                  .
gi 1016149547 131 R 131
Cdd:cd05346    78 D 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  47 ELTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRrclENGNLKekdilVLPLDLTDTGSHEAATKAVL 126
Cdd:COG3967     2 KLTGNTILITGGTSGIGLALAKRLHARGNTVIITGRREEKLEEAAA---ANPGLH-----TIVLDVADPASIAALAEQVT 73

                  ....*
gi 1016149547 127 QEFGR 131
Cdd:COG3967    74 AEFPD 78

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  55 VTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLE-NGNLKekdILVLPLDLTDtgsHEAATKAvlqefgrgf 133
Cdd:PRK08251    7 ITGASSGLGAGMAREFAAKGRDLALCARRTDRLEELKAELLArYPGIK---VAVAALDVND---HDQVFEV--------- 71

                          90
                  ....*....|....*.
gi 1016149547 134 FNGLRTELATYPGIIV 149
Cdd:PRK08251   72 FAEFRDELGGLDRVIV 87

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  47 ELTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNlkekdILVLPLDLTDTGSHEAATKAVL 126
Cdd:PRK07326    3 SLKGKVALITGGSKGIGFAIAEALLAEGYKVAITARDQKELEEAAAELNNKGN-----VLGLAADVRDEADVQRAVDAIV 77

                  ....*
gi 1016149547 127 QEFGR 131
Cdd:PRK07326   78 AAFGG 82

SDR family oxidoreductase;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1016149547  53 VWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGnlkekDILVLPLDLTDTGSHEAATKAVLQEFG 130
Cdd:PRK07024    5 VFITGASSGIGQALAREYARQGATLGLVARRTDALQAFAARLPKAA-----RVSVYAADVRDADALAAAAADFIAAHG 77

classical (c) SDR, subgroup 3; These proteins are members of the classical SDR family, with a canonical active site triad (and also active site Asn) and a typical Gly-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes 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 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNlkekDILVLPLDLTDTGSHEAATKAVLQEFGR 131
Cdd:cd05360     2 VVVITGASSGIGRATALAFAERGAKVVLAARSAEALHELAREVRELGG----EAIAVVADVADAAQVERAADTAVERFGR 77

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 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVkrrcLENGNLKEKDILVLPLDLTDTGSHEAATKAVLQEFGR 131
Cdd:cd05333     2 VALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAET----VEEIKALGGNAAALEADVSDREAVEALVEKVEAEFGP 77

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  42 RRPEWELTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLEngnlkEKDILVLPLDLTDTGSHEAA 121
Cdd:PRK05872    1 GPPMTSLAGKVVVVTGAARGIGAELARRLHARGAKLALVDLEEAELAALAAELGG-----DDRVLTVVADVTDLAAMQAA 75

                          90
                  ....*....|
gi 1016149547 122 TKAVLQEFGR 131
Cdd:PRK05872   76 AEEAVERFGG 85

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNlkekDILVLPLDLTDTGSHEAATKAVLQ 127
Cdd:PRK07109    6 IGRQVVVITGASAGVGRATARAFARRGAKVVLLARGEEGLEALAAEIRAAGG----EALAVVADVADAEAVQAAADRAEE 81

                  ....
gi 1016149547 128 EFGR 131
Cdd:PRK07109   82 ELGP 85

HetN oxidoreductase-like, classical (c) SDR; This subgroup includes Anabaena sp. strain PCC 7120 HetN, a putative oxidoreductase involved in heterocyst differentiation, and related proteins. 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 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRclengnlkEKDILVLPLDLTDTGSHEAATKAVLQEFGR 131
Cdd:cd08932     2 VALVTGASRGIGIEIARALARDGYRVSLGLRNPEDLAALSAS--------GGDVEAVPYDARDPEDARALVDALRDRFGR 73

SDR family oxidoreductase;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1016149547  47 ELTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNlkekDILVLPLDLTDTGSHEAA 121
Cdd:PRK06949    6 NLEGKVALVTGASSGLGARFAQVLAQAGAKVVLASRRVERLKELRAEIEAEGG----AAHVVSLDVTDYQSIKAA 76

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNlkEKDILVLPLDLTDTGSHEAATKAVLQ 127
Cdd:cd05330     1 FKDKVVLITGGGSGLGLATAVRLAKEGAKLSLVDLNEEGLEAAKAALLEIAP--DAEVLLIKADVSDEAQVEAYVDATVE 78

                          90
                  ....*....|
gi 1016149547 128 EFGR--GFFN 135
Cdd:cd05330    79 QFGRidGFFN 88

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRcLENGnlkEKDILVlPLDLTDTGSHEAATKAVLQ 127
Cdd:PRK07231    3 LEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAE-ILAG---GRAIAV-AADVSDEADVEAAVAAALE 77

                  ....
gi 1016149547 128 EFGR 131
Cdd:PRK07231   78 RFGS 81

gluconate 5-dehydrogenase (Ga5DH)-like, classical (c) SDRs; Ga5DH catalyzes the NADP-dependent conversion of carbon source D-gluconate and 5-keto-D-gluconate. This SDR subgroup has a classical Gly-rich NAD(P)-binding motif and a conserved active site tetrad pattern. However, it has been proposed that Arg104 (Streptococcus suis Ga5DH numbering), as well as an active site Ca2+, play a critical role in catalysis. In addition to Ga5DHs this subgroup contains Erwinia chrysanthemi KduD which is involved in pectin degradation, and is a putative 2,5-diketo-3-deoxygluconate dehydrogenase. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107,15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGnlkeKDILVLPLDLTDTGSHEAATKAVLQ 127
Cdd:cd05347     3 LKGKVALVTGASRGIGFGIASGLAEAGANIVINSRNEEKAEEAQQLIEKEG----VEATAFTCDVSDEEAIKAAVEAIEE 78

                  ....
gi 1016149547 128 EFGR 131
Cdd:cd05347    79 DFGK 82

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENgnlkEKDILVLPLDLTDTGSHEAATKAVLQEFGR 131
Cdd:PRK07677    3 VVIITGGSSGMGKAMAKRFAEEGANVVITGRTKEKLEEAKLEIEQF----PGQVLTVQMDVRNPEDVQKMVEQIDEKFGR 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHE-LERVKRRCLENGnlkeKDILVLPLDLTDTGSHEAATKAVLQEFG 130
Cdd:PRK12825    8 VALVTGAARGLGRAIALRLARAGADVVVHYRSDEEaAEELVEAVEALG----RRAQAVQADVTDKAALEAAVAAAVERFG 83

                  .
gi 1016149547 131 R 131
Cdd:PRK12825   84 R 84

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGnlkekDILVLPLDLTDTGSHEAATKAVLQ 127
Cdd:PRK06138    3 LAGRVAIVTGAGSGIGRATAKLFAREGARVVVADRDAEAAERVAAAIAAGG-----RAFARQGDVGSAEAVEALVDFVAA 77

                  ....
gi 1016149547 128 EFGR 131
Cdd:PRK06138   78 RWGR 81

ketoreductase (KR) and fatty acid synthase (FAS), complex (x) SDRs; Ketoreductase, a module of the multidomain polyketide synthase (PKS), has 2 subdomains, each corresponding to a SDR family monomer. The C-terminal subdomain catalyzes the NADPH-dependent reduction of the beta-carbonyl of a polyketide to a hydroxyl group, a step in the biosynthesis of polyketides, such as erythromycin. The N-terminal subdomain, an interdomain linker, is a truncated Rossmann fold which acts to stabilizes the catalytic subdomain. Unlike typical SDRs, the isolated domain does not oligomerize but is composed of 2 subdomains, each resembling an SDR monomer. The active site resembles that of typical SDRs, except that the usual positions of the catalytic Asn and Tyr are swapped, so that the canonical YXXXK motif changes to YXXXN. Modular PKSs are multifunctional structures in which the makeup recapitulates that found in (and may have evolved from) FAS. In some instances, such as porcine FAS, an enoyl reductase (ER) module is inserted between the sub-domains. Fatty acid synthesis occurs via the stepwise elongation of a chain (which is attached to acyl carrier protein, ACP) with 2-carbon units. Eukaryotic systems consist of large, multifunctional synthases (type I) while bacterial, type II systems, use single function proteins. Fungal fatty acid synthase uses a dodecamer of 6 alpha and 6 beta subunits. In mammalian type FAS cycles, ketoacyl synthase forms acetoacetyl-ACP which is reduced by the NADP-dependent beta-KR, forming beta-hydroxyacyl-ACP, which is in turn dehydrated by dehydratase to a beta-enoyl intermediate, which is reduced by NADP-dependent beta-ER. Polyketide synthesis also proceeds via the addition of 2-carbon units as in fatty acid synthesis. The complex SDR NADP-binding motif, GGXGXXG, is often present, but is not strictly conserved in each instance of the module. 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 KRs 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 1016149547  48 LTDMVVWVTGASSGIGEELAYQLSKLGV-SLVLSARRVHELERVKR-RCLENGNLkekDILVLPLDLTDtgshEAATKAV 125
Cdd:cd05274   148 GLDGTYLITGGLGGLGLLVARWLAARGArHLVLLSRRGPAPRAAARaALLRAGGA---RVSVVRCDVTD----PAALAAL 220

                  ....*..
gi 1016149547 126 LQEFGRG 132
Cdd:cd05274   221 LAELAAG 227

17-beta-hydroxysteroid dehydrogenases (17beta-HSDs) types -1, -3, and -12, -like, classical (c) SDRs; This subgroup includes various 17-beta-hydroxysteroid dehydrogenases and 3-ketoacyl-CoA reductase, these are members of the SDR family, and contain the canonical active site tetrad and glycine-rich NAD-binding motif of the classical SDRs. 3-ketoacyl-CoA reductase (KAR, aka 17beta-HSD type 12, encoded by HSD17B12) acts in fatty acid elongation; 17beta- hydroxysteroid dehydrogenases are isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. 17beta-estradiol dehydrogenase (aka 17beta-HSD type 1, encoded by HSD17B1) converts estrone to estradiol. Estradiol is the predominant female sex hormone. 17beta-HSD type 3 (aka testosterone 17-beta-dehydrogenase 3, encoded by HSD17B3) catalyses the reduction of androstenedione to testosterone, it also accepts estrogens as substrates. This subgroup also contains a putative steroid dehydrogenase let-767 from Caenorhabditis elegans, mutation in which results in hypersensitivity to cholesterol limitation. 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 1016149547  55 VTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNLKEKDILVlplDLTDtgsheaatkavlqefGRGFF 134
Cdd:cd05356     6 VTGATDGIGKAYAEELAKRGFNVILISRTQEKLDAVAKEIEEKYGVETKTIAA---DFSA---------------GDDIY 67

                          90
                  ....*....|....*...
gi 1016149547 135 NGLRTELATYP-GIIVSN 151
Cdd:cd05356    68 ERIEKELEGLDiGILVNN 85

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1016149547  47 ELTDMVVWVTGASSGIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNlkeKDILVLPLDLTD 114
Cdd:cd05343     3 RWRGRVALVTGASVGIGAAVARALVQHGMKVVGCARRVDKIEALAAECQSAGY---PTLFPYQCDLSN 67

3-keto steroid reductase, classical (c) SDRs; 3-keto steroid reductase (in concert with other enzymes) catalyzes NADP-dependent sterol C-4 demethylation, as part of steroid biosynthesis. 3-keto reductase is a classical SDR, with a well conserved canonical active site tetrad and fairly well conserved characteristic 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 1016149547  52 VVWVTGASSGIGEELAYQL-----SKLGVSLVLSARRVHELERVKRRCLENGNLKEKDILVLPLDLTDTGSHEAATKAVL 126
Cdd:cd08941     3 VVLVTGANSGLGLAICERLlaeddENPELTLILACRNLQRAEAACRALLASHPDARVVFDYVLVDLSNMVSVFAAAKELK 82

                          90       100
                  ....*....|....*....|.
gi 1016149547 127 QEFGRGFFNGLRTELATYPGI 147
Cdd:cd08941    83 KRYPRLDYLYLNAGIMPNPGI 103

rhamnulose-1-phosphate aldolase/alcohol dehydrogenase, classical (c) SDRs; This family has bifunctional proteins with an N-terminal aldolase and a C-terminal classical SDR domain. One member is identified as a rhamnulose-1-phosphate aldolase/alcohol dehydrogenase. The SDR domain has a canonical SDR glycine-rich NAD(P) binding motif and a match to the characteristic active site triad. However, it lacks an upstream active site Asn typical of 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 1016149547  52 VVWVTGASSGIGEELAYQLSKLGVSLVL------SARRVHELERVKRRclengnlkekdILVLPLDLTDTGSHEAATKAV 125
Cdd:cd08943     3 VALVTGGASGIGLAIAKRLAAEGAAVVVadidpeIAEKVAEAAQGGPR-----------ALGVQCDVTSEAQVQSAFEQA 71