2V6F,2V6G


Conserved Protein Domain Family
5beta-POR_like_SDR_a

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cd08948: 5beta-POR_like_SDR_a 
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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.
Statistics
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PSSM-Id: 187652
Aligned: 89 rows
Threshold Bit Score: 272.582
Created: 1-Apr-2010
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
active siteNAD(P) binding
Conserved site includes 2 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:This K and Y are critical active site residues in Digitalis lanata progesterone 5beta-reductase, they are in an atypical location for an SDR
  • Comment:This group lacks the SDR canonical active site tetrad (YXXXK motif and upstream S, N)
  • Citation:PMID 7742302

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                     
2V6F_A      3 VALIVGVTGIIGNSLAEILPLadt----pggPWKVYGVARRTrpaw---------hedNPINYVQCDISDPDDs------ 63  wooly foxglove
2V6G_A      3 VALIVGVTGIIGNSLAEILPLadt----pggPWKVYGVARRTrpaw---------hedNPINYVQCDISDPDDs------ 63  Digitalis lanata
EAW17026    7 HALIFGASGISGWSLMKQCLSypt----pstFAHITGLCNRPadkqsl----mlpddpRLNIVSGIDLTAPHErvv-sel 77  Neosartorya fische...
EED20906    7 HAVVFGCSGINGWALVNQLLSgyps---agaFSKITAIANRPftahea----rwpadnRLQIVSGIDLLARDDaqiskal 79  Talaromyces stipit...
EEU33952    8 VALIFGASGISGWALMRECLSfps----tetFSRVIGLSHRPlskeaa----rlpndpRLELNNGLDLTHGGQtk---ek 76  Nectria haematococ...
CAP85777    7 VALVFGASGISGWAVTKCALSypt----pttFDRVIGLTNRPlplers----glphdpRLELHCGVNLRGNLDevl-cql 77  Penicillium chryso...
CAK96763    8 HAIVYGASGLIGWALINQLLSpypv---adtFKKVTAVTNRPldlsetywpeadshrpRLQLASGVDLRSWDRdrlvewl 84  Aspergillus niger ...
CAK42986    9 VALVFGASGISGWAVTRSLLEypt----rstFSRVIGLTHRPqtrvql----glpddpRLEVYSGINLRGSLDevm-tqm 79  Aspergillus niger ...
AAS92550   12 TALVYGATGVTGWGLCKNLLEqqadsastptFSRVIGVCKQPaqdlgl-----fledkRFELVDGVDLLQGEDsvv--ev 84  blackleg of rapese...
EEY16567    6 HALVFGAAGLLGWAAVDQLLSgypa---pqtFSQVTAVINRPvaeaalhwpaasstrpKLHIASGINLLDGDAdalarql 82  Verticillium albo-...
Feature 1                                                                        #            
2V6F_A     64 QAKLSPLTDVTHVFYVTWANrst----eqENCEANSKMFRNVLDAVIPncpnLKHISLQTGr-----KHYMGPFesygki 134 wooly foxglove
2V6G_A     64 QAKLSPLTDVTHVFYVTWANrst----eqENCEANSKMFRNVLDAVIPncpnLKHISLQTGr-----KHYMGPFesygki 134 Digitalis lanata
EAW17026   78 KKKVPSVEEVDIVFFCAYIQtnd----haSLREVNTALLKTAVQAITTaskkVSTIILQTGg-----KGYGLEFpdnvpi 148 Neosartorya fische...
EED20906   80 ADKVSSVETVSHIYYAAYRAsdi----paEECRTNKEMLRAAVQSIEClsskLSFVTLITGt-----KAYGVYLldkfpy 150 Talaromyces stipit...
EEU33952   77 LGSLPGIGDVTHVYFDVVKVn--------ATIVDNALIALNELCPMMEf---FGYGTVGFGwppapwKEDLPRMp----- 140 Nectria haematococ...
CAP85777   78 QEKVPSLEDVTHVYYLAYSNataysidvmAIRDINEGMTYNAVHAVDRlcknMKFFVLQTGt-----NNYGVAVfrfqeh 152 Penicillium chryso...
CAK96763   85 RQVVEDSQGVTHVYYLVFTAmdd----dlEEVATNRRMLQNVIDAHNLispkLQFVSFVGGt-----RGYGIYSpggtfi 155 Aspergillus niger ...
CAK42986   80 RETIPQLDQVTHVYYLAYSNataytenvmDIKDINVVMTYNAVHACDTlcknMTFFVLQTGt-----NHYGVAAfqhidk 154 Aspergillus niger ...
AAS92550   85 LKEVKGIENVTHVFYVANRNspsd--gpdERISFNVKMIQSAVKAAEQlssnMQVLIMQTSi-----NVYGIFAslmggt 157 blackleg of rapese...
EEY16567   83 REKAPGIEKVTHAFYFVFSPvnd---dhrEECRVNCGMMQRVTDALNLlcpqLKSIVYAGGt-----RGYGIYNpggtft 154 Verticillium albo-...
Feature 1                            #                                                        
2V6F_A    135 esh----dppytedlPRLKYMNFYYDLEDIMLEEVEKKEgl--tWSVHRPGNIFGFsp-ySMMNLVGTLCVYAAICkh-- 205 wooly foxglove
2V6G_A    135 esh----dppytedlPRLKYMNFYYDLEDIMLEEVEKKEgl--tWSVHRPGNIFGFsp-ySMMNLVGTLCVYAAICkh-- 205 Digitalis lanata
EAW17026  149 ktp---lhedlpripEPYRSKIFYYDQYDLLDKMTQEAGct-wtFSDIRPDGIVGFapgsNAMNMAHGIAFYLSIYrevf 224 Neosartorya fische...
EED20906  151 rgqi-plredlprvpVEYAKDLFYYHQVDLLHEISEGKSw---sWCEIRPDIIVGVapfgNANCMAQTMGIYIGVYrale 226 Talaromyces stipit...
EEU33952  141 ---------------EPYASDIFYYAQYDVVARHAANKSw---gWSEIRPSYLVRFvphhNAMNVAQSLGLFLSYYrsmk 202 Nectria haematococ...
CAP85777  153 ieinpplhednpripSPWGDEIFYYAQVDIIKEANKGKSw---kWCEVRPDQIIGHvptpTSMTYVEPLALYLTLYrhvn 229 Penicillium chryso...
CAK96763  156 ppl---heelvnnlpPDYAKTVVYPAYREILSTSSQGRN-----WTWCEVGFTPNG----SQFSLALHWAQYLSLYaynn 223 Aspergillus niger ...
CAK42986  155 ltfntplredaprvpSPYGDEIFYYGQVDLIREAAQGKSwrwanEKSTYPGHVPST----TSMTTVEPIALYLSLYryvy 230 Aspergillus niger ...
AAS92550  158 ltcpsplvesadrtpSPYREMDVHYAQCDELKRLSKGKSw---sWFEVRPDAVIGYvprrHENNFTVSLGLFLATYahvh 234 blackleg of rapese...
EEY16567  155 apl---vesmagtlpEDYAKTVAYPWFRQILTRASRGRSw---tWTEVCPDAVVGFspngSAFSLALHWAQYLSLYrlnn 228 Verticillium albo-...
Feature 1                                                                                     
2V6F_A    206 -----------egKVLRFTGckaaWDGYSDCSDAd--LIAEHHIWAAVDPy--AKNEAFNVSNGDVFk-WKHFWKVLAEQ 269 wooly foxglove
2V6G_A    206 -----------egKVLRFTGckaaWDGYSDCSDAd--LIAEHHIWAAVDPy--AKNEAFNVSNGDVFk-WKHFWKVLAEQ 269 Digitalis lanata
EAW17026  225 ----------gegTKVPFPGn--kRGYYSKHSDTfqdLLSKMEIYAAVNRdkcGNGSVFNVADGEAVt-WAGVWPGICEY 291 Neosartorya fische...
EED20906  227 ----------gegARVPFPGn--eTTWRLTNTDSnqdIIARFCIYASFQPrekVHTRAFNIADGKTPvsWSQRWPILAKY 294 Talaromyces stipit...
EEU33952  203 ----------gagAECVFPGtpdsWTALRTESAQd--LVAHFHIHVSLHTd-kSSGRSFNVGDGDPVs-WELTWPVLCEY 268 Nectria haematococ...
CAP85777  230 ----------glgASVVFPGs--yPNYTHTFTASsqdIIARSELYLSVEKpdrGHGEAFNTADNDIPasWALVWPKMCEY 297 Penicillium chryso...
CAK96763  224 gigphtqgsakpaVEVPFPGsiagATSLFTPVSSn--RLARFMIFASLHPetcGGGRLFNVADQPTPctYGSLWPRLAEW 301 Aspergillus niger ...
CAK42986  231 ----------gygATVPFPGt--pTNYVYTFTDSsqdIISRAEIYLSVVKpdeANGEAFNIADTATPgpWCVKWPILAEY 298 Aspergillus niger ...
AAS92550  235 ----------gagAPVRFPGtpesWKCKFSMVSQd--QLARFEIHLATHAeglQSGEAFNVSNGDVLt-WSKLWPEAAAR 301 blackleg of rapese...
EEY16567  229 a--------ssgeVEVPFPGseagSDALFTPVSSr--TLGRISVHAALHPa-eCGGKIVNMADRARPttFRELWPGIAGW 297 Verticillium albo-...
Feature 1                                                                                
2V6F_A    270 FGVECGEYeegvdlklq---dlmkgkepvWEEIVRENGltptkl-----------------kdvgiWWFGDVILG 324 wooly foxglove
2V6G_A    270 FGVECGEYeegvdlklq---dlmkgkepvWEEIVRENGltptkl-----------------kdvgiWWFGDVILG 324 Digitalis lanata
EAW17026  292 FGLMGVEPeevke------------kkesMEEFVQGHMk--------------------------eWQRLVEKYG 328 Neosartorya fischeri NR...
EED20906  295 FGLEGVGPdss---------------slhPTEYMDCHWs--------------------------eLQALCRKRG 328 Talaromyces stipitatus ...
EEU33952  269 FGLKGVGPlahke-----------geiygIEWLMAQKEs---------------------------WPDWIQEQG 305 Nectria haematococca mp...
CAP85777  298 FGLRGEGPspedk------------gwkdIDKWWFAHQd--------------------------dYKKMCKKYG 334 Penicillium chrysogenum...
CAK96763  302 FGLVGVPPvdpapegehn-klkvgevperASTLAPGEYit-------------------------kYREIFTRYG 350 Aspergillus niger CBS 5...
CAK42986  299 FGLKAIRPtqtd--------------yaaIDKWWYDHQd--------------------------dYDRMCKEYG 333 Aspergillus niger CBS 5...
AAS92550  302 FGLRGVGPegageeegkgeaeggakgatgWSWPLGDETtm------------------------kkWEEENQVQK 352 blackleg of rapeseed fu...
EEY16567  298 FGLIGVGPeada-------------aalkPGEYVEKHKrlfatrgladaaekgvgagsvqldsvgwWLTFDRQLS 359 Verticillium albo-atrum...

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