3GPI,3IUS


Conserved Protein Domain Family
SDR_a4

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cd05266: SDR_a4 
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atypical (a) SDRs, subgroup 4
Atypical SDRs in this subgroup are poorly defined, one member is identified 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 related to, but is different from, the archetypical SDRs, GXGXXG. This subgroup also lacks most of the characteristic active site residues of the SDRs; however, the upstream Ser is present at the usual place, and some potential catalytic residues are present in place of the usual YXXXK active site 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. 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.
Statistics
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PSSM-Id: 187576
Aligned: 33 rows
Threshold Bit Score: 195.232
Created: 22-Sep-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
putative NAD(P)
Conserved site includes 19 residues -Click on image for an interactive view with Cn3D
Feature 1:putative NAD(P) binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1           # ###                  ###                                                  
3GPI_A        6 ILIAGCGDLGLELARRLTAqGHEVTGLRRSaqpm----------------------pagvQTLIADVtrpdtla------ 57  Methylobacillus ...
AAF41222      9 ISITGLGYLGLPLAQKFYQhGSRVAAVKRSltsddinlpihld-----tidlnqdsafqsANLARDTsfwrh-------- 75  Neisseria mening...
NP_934158     4 ILIIGAGWLGLPFAQQLSAlKHQVIVTRRStds------------------------lreVPLAQESkaildlanddaak 59  Vibrio vulnificu...
AAC75077      4 VAIVGLGWLGMPLAMSLSArGWQVTGSKTTqdgveaarms----------gidsyllrmePELVCDSddlda-------- 65  Escherichia coli...
CAE07875      5 FGVVGCGYVGSAVALHLRAqGYELMGTTTGparlaelcdlvdh-----prilragdsaadFSVIDDL------------- 66  Synechococcus sp...
YP_008161     3 IGILGCGYVGQAAAVFWKNqSHFLTVTTRQiekinfl----------------qtfahqvHQLTDDNilpf--------- 57  Candidatus Proto...
YP_267653    14 VGIIGCGWLGSALAYQLKNqDIAVLATRSNid--------------------------niEQLKSQGi------------ 55  Colwellia psychr...
ZP_01450004   8 VMLCGCGWLGQPLASRLISqGIKVYGTTTRtcqlsflnelgitphlfsisknsedspefnPSLLADLak----------- 76  alpha proteobact...
ZP_01133460  10 CVILGHGWLGQDLKQQLIGkKYGVDATVRDpekaeq-------------------lglqyFSLSNEVlnhni-------- 62  Pseudoalteromona...
YP_446112     6 VSILGCGWLGRPLAQHLVAqDVRVRGSTTTpe--------------------------kvDALREDGvepylltltpel- 58  Salinibacter rub...
Feature 1                       ###                                                      ###    
3GPI_A       58 ----sivhlrpEILVYCVAAseysd------------ehyrlSYVEGLRNTLSALEgap--------lqHVFFVSSTGVY 113 Methylobacillus ...
AAF41222     76 -------hankPVWFCLLPP----------------------SSLTHYADTVKQWAelara----cnvqHLIFTSSTSVY 122 Neisseria mening...
NP_934158    60 kvrelvdnnaiDIVVGSFPPgf------------------rkGSGEEYAHQWQKIVdgikd----savqKVIMVSSTTVY 117 Vibrio vulnificu...
AAC75077     66 -------lmdaDALVITLPAr---------------------RSGPGDEFYLQAVQelvdsa-lahripRIIFTSSTSVY 116 Escherichia coli...
CAE07875     67 -----------DGVLIAMAPttasye----------edqyraVYAEAVPALVKALRerpr-----qrplHVSYLSSAGVY 120 Synechococcus sp...
YP_008161    58 -------lanqDILLVSVAAassr--------------dyqnTYLETARRIIELLPqtp-------slkQIIYTGSTSVY 109 Candidatus Proto...
YP_267653    56 -----------EAEVLSLPAeqaqlnthpifkqqclviaitpQFRQGRVDYADKVQqlvesakvgncveQIILLSSSAIY 124 Colwellia psychr...
ZP_01450004  77 ----------cDVLVINIPPgrrdl-------------dansFTQNMLRLFKTAMTqqp--------dvRIIFVSTTSVF 125 alpha proteobact...
ZP_01133460  63 -------eckdAYWVCCIPPgf------------------rrEESNYLTVLAAALKlaqs-----qamkGFLLCSSTGIY 112 Pseudoalteromona...
YP_446112    59 tgedesaffasPILVLNVPPsrt-----------------adDAKAHYRRQIDAVReaaah----gaveWVLFASSTGVY 117 Salinibacter rub...
Feature 1                                 #   #                                    ####         
3GPI_A      114 GQevEEWLDEdtppi-------akdfSGKRMLEAEALLAAYs--------------------STILRFSGIYGPGRLrmi 166 Methylobacillus ...
AAF41222    123 GDtaRECDEIalpd--------pqteSARQILAAEQHLLDSgv-----------------pnIDILRLGGLYCAERHpvg 177 Neisseria mening...
NP_934158   118 PNqpVEMREDdatlakanrenalfsdKARVMLQAEQSLLDSgk------------------nFTILRLSGLFGPHRHpar 179 Vibrio vulnificu...
AAC75077    117 GDaqGTVKETtprn--------pvtnSGRVLEELEDWLHNLpg-----------------tsVDILRLAGLVGPGRHpgr 171 Escherichia coli...
CAE07875    121 GDqsGAVTTElsspd-------lsntTNELLVQAENAVLALntp---------------siqTCVLRLGGIYGPGKDips 178 Synechococcus sp...
YP_008161   110 GDfqGNWVDEttlln-------plneQSYCLSQTEQFFLKApss----------------vnVTIFRLGEIYGPGRWitd 166 Candidatus Proto...
YP_267653   125 NGlsGDVEENsild--------msadKVSVLNQAEQAVLSFnhpgrnesrlnalnaevgnkkAYVLRLSGLVGPKRHpgk 196 Colwellia psychr...
ZP_01450004 126 GDvtGQVDEDtpta--------pvtaSGIAHQTLEHWLLKHas-----------------kqSTIVRLAGLINQTRHpvt 180 alpha proteobact...
ZP_01133460 113 PSqaGLFHEQssln--------dlnlKQQGLLEAEQLVLSSg-------------------lGKVVRLAGLMGPKRHpgr 165 Pseudoalteromona...
YP_446112   118 PTveRTVTEAdqppgrpdalpgtrrsTGRAVLAAEERLMRDss-----------------faTTIVRFGGLYGGDRHpgr 180 Salinibacter rub...
Feature 1                                                                                       
3GPI_A      167 rqaqtpe--qwparnawtNRIHRDDGAAFIAYLIQqrshavpeRLYIVTDNQPlpvhdllrWLADRQGIAYPagatp--- 241 Methylobacillus ...
AAF41222    178 rlvqkq---nipggnrpiNIVHRNIAVESLFQTAFnpg---grRLKNIIEPRHptrrefytEEAAKLGLPAPdfapd--- 248 Neisseria mening...
NP_934158   180 fvphlk----qissrapaNMLHLDDAINALLFALSaa----dqQVLNVSTPTTvdkatfyqAALESAQLDVDfppvv--- 248 Vibrio vulnificu...
AAC75077    172 ffagkt----apdgehgvNLVHLEDVIGAITLLLQapk---ggHIYNICAPAHparnvfypQMARLLGLEPPqfrnsl-- 242 Escherichia coli...
CAE07875    179 firsasgqqvakngnhinAWVHLDDIVRGVEFALQrr----lqGIYNLVDDLQlsrrelsnALCDDEGLPPViwdnh--- 251 Synechococcus sp...
YP_008161   167 rvirmhqysfpgtgnqltNVIHLTDIVRALDFALQnk----lhGIFNLCNDFHiprklfyeQLLQSAHLPSIqwdankps 242 Candidatus Proto...
YP_267653   197 fllngh---mlkspqaivNLIHQQDAVGLIQTLLQsan---cgGIFNGVSSTKvtkkqyyqAAASALQLPTPtfeeiels 270 Colwellia psychr...
ZP_01450004 181 slvkrs---vieqghqvvNLVHQIDAVNGLLQVVLkwne-vvgHILHLCAPEHptredyyqAAAQSKQLPKL-------- 248 alpha proteobact...
ZP_01133460 166 fvagkq---lassanesvNMVHQRDASNAIVHILEnws--gaePIYNLVMADHsckadfyqQACKQLGTASPtfetd--- 237 Pseudoalteromona...
YP_446112   181 flagrs---digrpeapvNLIHQDDCVALLATLLDqna---qgEVFNACADAHptrqalytRAAEVLGLEPPtfdes--- 251 Salinibacter rub...
Feature 1                        
3GPI_A      242 pvqgnKKLSNARLLASG 258 Methylobacillus flagellatus KT
AAF41222    249 -dsvgKIIRTVCDNGLS 264 Neisseria meningitidis MC58
NP_934158   249 -avedKRIVVDKLLQSG 264 Vibrio vulnificus YJ016
AAC75077    243 dsgkgKIIDGSRICNEL 259 Escherichia coli K12
CAE07875    252 drpgaRGVQRSCLQCTA 268 Synechococcus sp. WH 8102
YP_008161   243 lhggnKKVSSSKLKKLG 259 Candidatus Protochlamydia amoebophila UWE25
YP_267653   271 ednapKVVSGKKTQAEL 287 Colwellia psychrerythraea 34H
ZP_01450004 249 -----KFISNDSESIHT 260 alpha proteobacterium HTCC2255
ZP_01133460 238 -hqveRIIDGSAIEQLG 253 Pseudoalteromonas tunicata D2
YP_446112   252 dpttgKRVDNQKVKDRC 268 Salinibacter ruber DSM 13855

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