Uncharacterized conserved protein YbjT, contains NAD(P)-binding and DUF2867 domains [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241   3 RALLVGATGLVGRELLQRLQSDPQitAIVAPTRTPLPPHGKLTNPVGDALFELL--SSLQ---QPVDLVFCCLGTtrrAA 77
Cdd:COG0702    1 KILVTGATGFIGRRVVRALLARGH--PVRALVRDPEKAAALAAAGVEVVQGDLDdpESLAaalAGVDAVFLLVPS---GP 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241  78 GSADAFRYVDYQLVVESAltgRRLGAQHCLVVSALGANADSTFLYNRTKGEMEQALREQHWPrLTLVRPSMLVGD--RPA 155
Cdd:COG0702   76 GGDFAVDVEGARNLADAA---KAAGVKRIVYLSALGADRDSPSPYLRAKAAVEEALRASGLP-YTILRPGWFMGNllGFF 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 896189241 156 PRLMERLTLPLFRlLPGKWRAVSAKDVAQTLLQQAFTPGEGVRVLE 201
Cdd:COG0702  152 ERLRERGVLPLPA-GDGRVQPIAVRDVAEAAAAALTDPGHAGRTYE 196

3,8-divinyl protochlorophyllide a 8-vinyl reductase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241   3 RALLVGATGLVG----RELLQRlqsDPQITAIVAP------------TRTPLPP----HGKLTNPvgDALFELLSSLQQP 62
Cdd:PLN02657  62 TVLVVGATGYIGkfvvRELVRR---GYNVVAVAREksgirgkngkedTKKELPGaevvFGDVTDA--DSLRKVLFSEGDP 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241  63 VDLVFCCLGTtrRAAGSADAFRyVDYQLVVESALTGRRLGAQHCLVVSALGANaDSTFLYNRTKGEMEQALRE-QHWPRL 141
Cdd:PLN02657 137 VDVVVSCLAS--RTGGVKDSWK-IDYQATKNSLDAGREVGAKHFVLLSAICVQ-KPLLEFQRAKLKFEAELQAlDSDFTY 212

                 ....*.
gi 896189241 142 TLVRPS 147
Cdd:PLN02657 213 SIVRPT 218

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, subunit 9, 39 kDa, (NDUFA9) -like, atypical (a) SDRs; This subgroup of extended SDR-like proteins are atypical SDRs. They have a glycine-rich NAD(P)-binding motif similar to the typical SDRs, GXXGXXG, and have the YXXXK active site motif (though not the other residues of the SDR tetrad). Members identified include NDUFA9 (mitochondrial) and putative nucleoside-diphosphate-sugar epimerase. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241   3 RALLVGATGLVGRELLQRLQSdpQITAIVAPTR-TPLPPHGKLTNPVGDALF--------ELLSSLQQPVDLVFCCLGtt 73
Cdd:cd05271    2 VVTVFGATGFIGRYVVNRLAK--RGSQVIVPYRcEAYARRLLVMGDLGQVLFvefdlrddESIRKALEGSDVVINLVG-- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241  74 RRAAGSADAFRYVDYQLVVESALTGRRLGAQHCLVVSALGANADSTFLYNRTKGEMEQALREQHwPRLTLVRPSMLVG-- 151
Cdd:cd05271   78 RLYETKNFSFEDVHVEGPERLAKAAKEAGVERLIHISALGADANSPSKYLRSKAEGEEAVREAF-PEATIVRPSVVFGre 156

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 896189241 152 DRPAPRL-MERLTLPLFRLLPG---KWRAVSAKDVAQTLLQQAFTP 193
Cdd:cd05271  157 DRFLNRFaKLLAFLPFPPLIGGgqtKFQPVYVGDVAEAIARALKDP 202

Extended (e) and atypical (a) SDRs; Extended or atypical short-chain dehydrogenases/reductases (SDRs, aka tyrosine-dependent oxidoreductases) are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241   4 ALLVGATGLVGRELLQRL-QSDPQITAIVAPTRTPLPPHGKLTN-PVGDALFEL-LSSLQQPVDLVFCCLGTTRraagSA 80
Cdd:cd05226    1 ILILGATGFIGRALARELlEQGHEVTLLVRNTKRLSKEDQEPVAvVEGDLRDLDsLSDAVQGVDVVIHLAGAPR----DT 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241  81 DAFR--YVDYQLVVESALtgRRLGAQHCLVVSALGA--------NADSTFLYNRTKGEMEQALREQhWPRLTLVRPSMLV 150
Cdd:cd05226   77 RDFCevDVEGTRNVLEAA--KEAGVKHFIFISSLGAygdlheetEPSPSSPYLAVKAKTEAVLREA-SLPYTIVRPGVIY 153

                 ..
gi 896189241 151 GD 152
Cdd:cd05226  154 GD 155

atypical (a) SDRs, subgroup 5; This subgroup contains atypical SDRs, some of which are identified as putative NAD(P)-dependent epimerases, one as a putative NAD-dependent epimerase/dehydratase. Atypical SDRs are distinct from classical SDRs. Members of this subgroup have a glycine-rich NAD(P)-binding motif that is very similar to the extended SDRs, GXXGXXG, and binds NADP. Generally, this subgroup has poor conservation of the active site tetrad; however, individual sequences do contain matches to the YXXXK active site motif, the upstream Ser, and there is a highly conserved Asp in place of the usual active site Asn throughout the subgroup. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241   3 RALLVGATGLVGRELLQRL-QSDPQITAIV-APTRTPLPPHGKLTNPVGDAlfELLSSLQ---QPVDLVFCCLGTTRRAA 77
Cdd:cd05243    1 KVLVVGATGKVGRHVVRELlDRGYQVRALVrDPSQAEKLEAAGAEVVVGDL--TDAESLAaalEGIDAVISAAGSGGKGG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241  78 GSADAfryVDYQ---LVVESAltgRRLGAQHCLVVSALGANADSTFL-----YNRTKGEMEQALREQHWPrLTLVRPSML 149
Cdd:cd05243   79 PRTEA---VDYDgniNLIDAA---KKAGVKRFVLVSSIGADKPSHPLealgpYLDAKRKAEDYLRASGLD-YTIVRPGGL 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 896189241 150 VGDRPAPRLmerltLPLFRLLPGKWRAVSAKDVAQTLLQQAFTPG 194
Cdd:cd05243  152 TDDPAGTGR-----VVLGGDGTRLDGPISRADVAEVLAEALDTPA 191

Nucleoside-diphosphate-sugar epimerase [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241   3 RALLVGATGLVGRELLQRLQSDP-QITAIV--APTRTPLPPHGKLTNPVGDAL-FELLSSLQQPVDLVFCCLGTTRRAAG 78
Cdd:COG0451    1 RILVTGGAGFIGSHLARRLLARGhEVVGLDrsPPGAANLAALPGVEFVRGDLRdPEALAAALAGVDAVVHLAAPAGVGEE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241  79 SADAFRYVDYQL---VVESAltgRRLGAQHCLVVSALGANADSTF------------LYNRTKGEMEQALRE---QHWPR 140
Cdd:COG0451   81 DPDETLEVNVEGtlnLLEAA---RAAGVKRFVYASSSSVYGDGEGpidedtplrpvsPYGASKLAAELLARAyarRYGLP 157

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 896189241 141 LTLVRPSMLVG---DRPAPRLMERL----TLPLFRLLPGKWRAVSAKDVAQTLLQQAFTPGEGVRV 199
Cdd:COG0451  158 VTILRPGNVYGpgdRGVLPRLIRRAlagePVPVFGDGDQRRDFIHVDDVARAIVLALEAPAAPGGV 223

Semialdehyde dehydrogenase, NAD binding domain; The semialdehyde dehydrogenase family is found in N-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in arginine biosynthesis, and aspartate-semialdehyde dehydrogenase, an enzyme involved in the biosynthesis of various amino acids from aspartate. This family is also found in yeast and fungal Arg5,6 protein, which is cleaved into the enzymes N-acety-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in arginine biosynthesis. All proteins in this entry contain a NAD binding region of semialdehyde dehydrogenase.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 896189241     6 LVGATGLVGRELLQRLQSDPQ--ITAIVAPTR---TPLPPHGKLTNPVGDALFELLSSLQQPVDLVFCCLG 71
Cdd:smart00859   4 IVGATGYVGQELLRLLAEHPDfeLTALAASSRsagKKVSEAGPHLKGEVVLELDPPDFEELAVDIVFLALP 74

UDP-glucose 4 epimerase, subgroup 4, extended (e) SDRs; UDP-glucose 4 epimerase (aka UDP-galactose-4-epimerase), is a homodimeric extended SDR. It catalyzes the NAD-dependent conversion of UDP-galactose to UDP-glucose, the final step in Leloir galactose synthesis. This subgroup is comprised of bacterial proteins, and includes the Staphylococcus aureus capsular polysaccharide Cap5N, which may have a role in the synthesis of UDP-N-acetyl-d-fucosamine. This subgroup has the characteristic active site tetrad and NAD-binding motif of the extended SDRs. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241   3 RALLVGATGLVGRELLQRLQSDPQItaIVAPTRTPLPphgKLTNPVGDALFELLSS--LQQPVDLVFCCLGTTR----RA 76
Cdd:cd05232    1 KVLVTGANGFIGRALVDKLLSRGEE--VRIAVRNAEN---AEPSVVLAELPDIDSFtdLFLGVDAVVHLAARVHvmndQG 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241  77 AGSADAFRYVDYQLVVESALTGRRLGAQHCLVVSALGANADSTFL--------------YNRTKGEMEQALRE---QHWP 139
Cdd:cd05232   76 ADPLSDYRKVNTELTRRLARAAARQGVKRFVFLSSVKVNGEGTVGapfdetdppapqdaYGRSKLEAERALLElgaSDGM 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 896189241 140 RLTLVRPSMLVG-DRPA--PRLME--RLTLPLFrllPGKWRA----VSAKDVAQTLLQQAFTPG 194
Cdd:cd05232  156 EVVILRPPMVYGpGVRGnfARLMRliDRGLPLP---PGAVKNrrslVSLDNLVDAIYLCISLPK 216

progesterone 5-beta-reductase-like proteins (5beta-POR), atypical (a) SDRs; 5beta-POR catalyzes the reduction of progesterone to 5beta-pregnane-3,20-dione in Digitalis plants. This subgroup of atypical-extended SDRs, shares the structure of an extended SDR, but has a different glycine-rich nucleotide binding motif (GXXGXXG) and lacks the YXXXK active site motif of classical and extended SDRs. Tyr-179 and Lys 147 are present in the active site, but not in the usual SDR configuration. Given these differences, it has been proposed that this subfamily represents a new SDR class. Other atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 896189241   4 ALLVGATGLVGRELLQRLQSDPQI-TAIVAPTRTPLPPHGK----------LTNPVGDALFELLSSLQQPVDLVFC 68
Cdd:cd08948    2 ALVVGATGISGWALVEHLLSDPGTwWKVYGLSRRPLPTEDDprlvehigidLLDPADTVLRAKLPGLEDVTHVFYA 77

dTDP-6-deoxy-L-lyxo-4-hexulose reductase and related proteins, extended (e) SDRs; dTDP-6-deoxy-L-lyxo-4-hexulose reductase, an extended SDR, synthesizes dTDP-L-rhamnose from alpha-D-glucose-1-phosphate, providing the precursor of L-rhamnose, an essential cell wall component of many pathogenic bacteria. This subgroup has the characteristic active site tetrad and NADP-binding motif. This subgroup also contains human MAT2B, the regulatory subunit of methionine adenosyltransferase (MAT); MAT catalyzes S-adenosylmethionine synthesis. The human gene encoding MAT2B encodes two major splicing variants which are induced in human cell liver cancer and regulate HuR, an mRNA-binding protein which stabilizes the mRNA of several cyclins, to affect cell proliferation. Both MAT2B variants include this extended SDR domain. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241   3 RALLVGATGLVGRELLQRLQSDPqITAIVAPTRTPLPPHGKLTNPvgDALFELLSSLqQPvDLVFCCLGTTRRAAGSAD- 81
Cdd:cd05254    1 KILITGATGMLGRALVRLLKERG-YEVIGTGRSRASLFKLDLTDP--DAVEEAIRDY-KP-DVIINCAAYTRVDKCESDp 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 896189241  82 --AFRY-VD--YQLVVESALTGRRL----------GAQHCLVVSALganADSTFLYNRTKGEMEQALREqHWPRLTLVRP 146
Cdd:cd05254   76 elAYRVnVLapENLARAAKEVGARLihistdyvfdGKKGPYKEEDA---PNPLNVYGKSKLLGEVAVLN-ANPRYLILRT 151

                 ....*.
gi 896189241 147 SMLVGD 152
Cdd:cd05254  152 SWLYGE 157

phenylcoumaran benzylic ether reductase (PCBER) like, atypical (a) SDRs; PCBER and pinoresinol-lariciresinol reductases are NADPH-dependent aromatic alcohol reductases, and are atypical members of the SDR family. Other proteins in this subgroup are identified as eugenol synthase. These proteins contain an N-terminus characteristic of NAD(P)-binding proteins and a small C-terminal domain presumed to be involved in substrate binding, but they do not have the conserved active site Tyr residue typically found in SDRs. Numerous other members have unknown functions. The glycine rich NADP-binding motif in this subgroup is of 2 forms: GXGXXG and G[GA]XGXXG; it tends to be atypical compared with the forms generally seen in classical or extended SDRs. The usual SDR active site tetrad is not present, but a critical active site Lys at the usual SDR position has been identified in various members, though other charged and polar residues are found at this position in this subgroup. Atypical SDR-related proteins retain the Rossmann fold of the SDRs, but have limited sequence identity and generally lack the catalytic properties of the archetypical members. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, 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.

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gi 896189241   5 LLVGATGLVGRELLQRLQSDP--QITAIVAPTRTP---LPPHGKLTNPVGDA-LFELLSSLQQpVDLVFCCLGTtrraAG 78
Cdd:cd05259    3 AIAGATGTLGGPIVSALLASPgfTVTVLTRPSSTSsneFQPSGVKVVPVDYAsHESLVAALKG-VDAVISALGG----AA 77

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gi 896189241  79 SADAFRYVD 87
Cdd:cd05259   78 IGDQLKLID 86