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 446741729   6 QGKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVeaeGVKAVIATADVSSYEEVTTAIETLKNGLGSI 85
Cdd:COG4221    4 KGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAEL---GGRALAVPLDVTDEAAVEAAVAAAVAEFGRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  86 DILINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVLG 165
Cdd:COG4221   81 DVLVNNAGVALLGPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRARGSGHIVNISSIAGLRPYPGGAVYAATKAAVRG 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 446741729 166 LTESLAMEVRKHNIRVTALTPSTVATDMAVDLGLTDGNPD-------KVMQAEDIAEFIVAQLKLNKRTFI 229
Cdd:COG4221  161 LSESLRAELRPTGIRVTVIEPGAVDTEFLDSVFDGDAEAAaavyeglEPLTPEDVAEAVLFALTQPAHVNV 231

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 446741729  10 ALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAkEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGSIDILI 89
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELA-AIEALGGNAVAVQADVSDEEDVEALVEEALEEFGRLDILV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  90 NNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVLGLTES 169
Cdd:cd05233   80 NNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGGRIVNISSVAGLRPLPGQAAYAASKAALEGLTRS 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 446741729 170 LAMEVRKHNIRVTALTPSTVATDMAVDLGLTDGNPD--------KVMQAEDIAEFIV 218
Cdd:cd05233  160 LALELAPYGIRVNAVAPGLVDTPMLAKLGPEEAEKElaaaiplgRLGTPEEVAEAVV 216

This enzymatic domain is part of bacterial polyketide synthases; It catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729    11 LITGAGRGIGRAVAIALAKEGV-NVGLLARS---EENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGSID 86
Cdd:smart00822   4 LITGGLGGLGRALARWLAERGArRLVLLSRSgpdAPGAAALLAELEAAGARVTVVACDVADRDALAAVLAAIPAVEGPLT 83

                           90       100
                   ....*....|....*....|...
gi 446741729    87 ILINNAGISKFGKFLELDVADWE 109
Cdd:smart00822  84 GVIHAAGVLDDGVLASLTPERFA 106

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 446741729   6 QGKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVeaeGVKAVIATADVSSYEEVTTAIETLKNGLGSI 85
Cdd:COG4221    4 KGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAEL---GGRALAVPLDVTDEAAVEAAVAAAVAEFGRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  86 DILINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVLG 165
Cdd:COG4221   81 DVLVNNAGVALLGPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRARGSGHIVNISSIAGLRPYPGGAVYAATKAAVRG 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 446741729 166 LTESLAMEVRKHNIRVTALTPSTVATDMAVDLGLTDGNPD-------KVMQAEDIAEFIVAQLKLNKRTFI 229
Cdd:COG4221  161 LSESLRAELRPTGIRVTVIEPGAVDTEFLDSVFDGDAEAAaavyeglEPLTPEDVAEAVLFALTQPAHVNV 231

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 446741729   5 LQGKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGS 84
Cdd:COG1028    4 LKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDAEALEAAAAELRAAGGRALAVAADVTDEAAVEALVAAAVAAFGR 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  85 IDILINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVL 164
Cdd:COG1028   84 LDILVNNAGITPPGPLEELTEEDWDRVLDVNLKGPFLLTRAALPHMRERGGGRIVNISSIAGLRGSPGQAAYAASKAAVV 163

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 446741729 165 GLTESLAMEVRKHNIRVTALTPSTVATDMAVDLGLTDGNPDKVM---------QAEDIAEFIV 218
Cdd:COG1028  164 GLTRSLALELAPRGIRVNAVAPGPIDTPMTRALLGAEEVREALAariplgrlgTPEEVAAAVL 226

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 446741729  10 ALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAkEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGSIDILI 89
Cdd:cd05233    1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEALAELA-AIEALGGNAVAVQADVSDEEDVEALVEEALEEFGRLDILV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  90 NNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVLGLTES 169
Cdd:cd05233   80 NNAGIARPGPLEELTDEDWDRVLDVNLTGVFLLTRAALPHMKKQGGGRIVNISSVAGLRPLPGQAAYAASKAALEGLTRS 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 446741729 170 LAMEVRKHNIRVTALTPSTVATDMAVDLGLTDGNPD--------KVMQAEDIAEFIV 218
Cdd:cd05233  160 LALELAPYGIRVNAVAPGLVDTPMLAKLGPEEAEKElaaaiplgRLGTPEEVAEAVV 216

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729   5 LQGKNALITGAGRGIGRAVAIALAKEGVNVGL-LARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLG 83
Cdd:PRK05557   3 LEGKVALVTGASRGIGRAIAERLAAQGANVVInYASSEAGAEALVAEIGALGGKALAVQGDVSDAESVERAVDEAKAEFG 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  84 SIDILINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGV 163
Cdd:PRK05557  83 GVDILVNNAGITRDNLLMRMKEEDWDRVIDTNLTGVFNLTKAVARPMMKQRSGRIINISSVVGLMGNPGQANYAASKAGV 162

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 446741729 164 LGLTESLAMEVRKHNIRVTALTPSTVATDMavdlglTDGNPDKVM-------------QAEDIAEFIV 218
Cdd:PRK05557 163 IGFTKSLARELASRGITVNAVAPGFIETDM------TDALPEDVKeailaqiplgrlgQPEEIASAVA 224

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 446741729   8 KNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGSIDI 87
Cdd:cd05333    1 KVALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEIKALGGNAAALEADVSDREAVEALVEKVEAEFGPVDI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  88 LINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVLGLT 167
Cdd:cd05333   81 LVNNAGITRDNLLMRMSEEDWDAVINVNLTGVFNVTQAVIRAMIKRRSGRIINISSVVGLIGNPGQANYAASKAGVIGFT 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 446741729 168 ESLAMEVRKHNIRVTALTPSTVATDMavdlglTDGNPDKVMQA 210
Cdd:cd05333  161 KSLAKELASRGITVNAVAPGFIDTDM------TDALPEKVKEK 197

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729   7 GKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAE----GVKAVIATADVSSYEEVTTAIETLKNGL 82
Cdd:cd08939    1 GKHVLITGGSSGIGKALAKELVKEGANVIIVARSESKLEEAVEEIEAEanasGQKVSYISADLSDYEEVEQAFAQAVEKG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  83 GSIDILINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFG 162
Cdd:cd08939   81 GPPDLVVNCAGISIPGLFEDLTAEEFERGMDVNYFGSLNVAHAVLPLMKEQRPGHIVFVSSQAALVGIYGYSAYCPSKFA 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 446741729 163 VLGLTESLAMEVRKHNIRVTALTPSTVATDMAVDLGLTD-------GNPDKVMQAEDIAEFIVAQLK 222
Cdd:cd08939  161 LRGLAESLRQELKPYNIRVSVVYPPDTDTPGFEEENKTKpeetkaiEGSSGPITPEEAARIIVKGLD 227

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729   3 ELLQGKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGL 82
Cdd:PRK07454   2 SLNSMPRALITGASSGIGKATALAFAKAGWDLALVARSQDALEALAAELRSTGVKAAAYSIDLSNPEAIAPGIAELLEQF 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  83 GSIDILINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFG 162
Cdd:PRK07454  82 GCPDVLINNAGMAYTGPLLEMPLSDWQWVIQLNLTSVFQCCSAVLPGMRARGGGLIINVSSIAARNAFPQWGAYCVSKAA 161

                        170       180
                 ....*....|....*....|....*....
gi 446741729 163 VLGLTESLAMEVRKHNIRVTALTPSTVAT 191
Cdd:PRK07454 162 LAAFTKCLAEEERSHGIRVCTITLGAVNT 190

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 446741729   5 LQGKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGS 84
Cdd:cd05347    3 LKGKVALVTGASRGIGFGIASGLAEAGANIVINSRNEEKAEEAQQLIEKEGVEATAFTCDVSDEEAIKAAVEAIEEDFGK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  85 IDILINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVL 164
Cdd:cd05347   83 IDILVNNAGIIRRHPAEEFPEAEWRDVIDVNLNGVFFVSQAVARHMIKQGHGKIINICSLLSELGGPPVPAYAASKGGVA 162

                        170       180       190
                 ....*....|....*....|....*....|
gi 446741729 165 GLTESLAMEVRKHNIRVTALTPSTVATDMA 194
Cdd:cd05347  163 GLTKALATEWARHGIQVNAIAPGYFATEMT 192

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729   4 LLQGKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGvKAVIATADVSSYEEVTTAIETLKNGLG 83
Cdd:PRK07231   2 RLEGKVAIVTGASSGIGEGIARRFAAEGARVVVTDRNEEAAERVAAEILAGG-RAIAVAADVSDEADVEAAVAAALERFG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  84 SIDILINNAGIS-KFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFG 162
Cdd:PRK07231  81 SVDILVNNAGTThRNGPLLDVDEAEFDRIFAVNVKSPYLWTQAAVPAMRGEGGGAIVNVASTAGLRPRPGLGWYNASKGA 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 446741729 163 VLGLTESLAMEVRKHNIRVTALTPSTVATDMAVDL--GLTDGNPDKVMQA---------EDIAE 215
Cdd:PRK07231 161 VITLTKALAAELGPDKIRVNAVAPVVVETGLLEAFmgEPTPENRAKFLATiplgrlgtpEDIAN 224

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729   7 GKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGSID 86
Cdd:PRK06181   1 GKVVIITGASEGIGRALAVRLARAGAQLVLAARNETRLASLAQELADHGGEALVVPTDVSDAEACERLIEAAVARFGGID 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  87 ILINNAGISKFGKFLEL-DVADWEKIIQVNLMGVYYATRAALPSMIEQQsGDIINISSTAGQKGAPVTSAYSASKFGVLG 165
Cdd:PRK06181  81 ILVNNAGITMWSRFDELtDLSVFERVMRVNYLGAVYCTHAALPHLKASR-GQIVVVSSLAGLTGVPTRSGYAASKHALHG 159

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 446741729 166 LTESLAMEVRKHNIRVTALTPSTVATDMAVDLGLTDGNP--------DKVMQAEDIAEFIVAQLKLNKRTFIKSA 232
Cdd:PRK06181 160 FFDSLRIELADDGVAVTVVCPGFVATDIRKRALDGDGKPlgkspmqeSKIMSAEECAEAILPAIARRKRLLVMSL 234

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  10 ALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGSIDILI 89
Cdd:cd05339    2 VLITGGGSGIGRLLALEFAKRGAKVVILDINEKGAEETANNVRKAGGKVHYYKCDVSKREEVYEAAKKIKKEVGDVTILI 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  90 NNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVLGLTES 169
Cdd:cd05339   82 NNAGVVSGKKLLELPDEEIEKTFEVNTLAHFWTTKAFLPDMLERNHGHIVTIASVAGLISPAGLADYCASKAAAVGFHES 161

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 446741729 170 LAMEVR---KHNIRVTALTPSTVATDMAVDLGLTDGNPDKVMQAEDIAEFIVAQLKLNKRTFI 229
Cdd:cd05339  162 LRLELKaygKPGIKTTLVCPYFINTGMFQGVKTPRPLLAPILEPEYVAEKIVRAILTNQQMLY 224

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR)-like, SDR; This subgroup resembles the SDR family, but does not have a perfect match to the NAD-binding motif or the catalytic tetrad characteristic of the SDRs. It includes the SDRs, Q9HYA2 from Pseudomonas aeruginosa PAO1 and APE0912 from Aeropyrum pernix K1. 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 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 446741729   7 GKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKNGLGSID 86
Cdd:cd05344    1 GKVALVTAASSGIGLAIARALAREGARVAICARNRENLERAASELRAGGAGVLAVVADLTDPEDIDRLVEKAGDAFGRVD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729  87 ILINNAGISKFGKFLELDVADWEKIIQVNLMGVYYATRAALPSMIEQQSGDIINISSTAGQKGAPVTSAYSASKFGVLGL 166
Cdd:cd05344   81 ILVNNAGGPPPGPFAELTDEDWLEAFDLKLLSVIRIVRAVLPGMKERGWGRIVNISSLTVKEPEPNLVLSNVARAGLIGL 160

                        170       180
                 ....*....|....*....|....*.
gi 446741729 167 TESLAMEVRKHNIRVTALTPSTVATD 192
Cdd:cd05344  161 VKTLSRELAPDGVTVNSVLPGYIDTE 186

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446741729   1 MAELLQGKNALITGAGRGIGRAVAIALAKEGVNVGLLARSEENLKAVAKEVEAEGVKAVIATADVSSYEEVTTAIETLKN 80
Cdd:PRK12939   1 MASNLAGKRALVTGAARGLGAAFAEALAEAGATVAFNDGLAAEARELAAALEAAGGRAHAIAADLADPASVQRFFDAAAA 80