2J8Z


Conserved Protein Domain Family
p53_inducible_oxidoreductase

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cd05276: p53_inducible_oxidoreductase 
Click on image for an interactive view with Cn3D
PIG3 p53-inducible quinone oxidoreductase
PIG3 p53-inducible quinone oxidoreductase, a medium chain dehydrogenase/reductase family member, acts in the apoptotic pathway. PIG3 reduces ortho-quinones, but its apoptotic activity has been attributed to oxidative stress generation, since overexpression of PIG3 accumulates reactive oxygen species. PIG3 resembles the MDR family member quinone reductases, which catalyze the reduction of quinone to hydroxyquinone. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site, and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine, the ribose of NAD, a serine, then the alcohol, which allows the transfer of a hydride to NAD+, creating NADH and a zinc-bound aldehyde or ketone. In yeast and some bacteria, the active site zinc binds an aldehyde, polarizing it, and leading to the reverse reaction.
Statistics
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PSSM-Id: 176180
View PSSM: cd05276
Aligned: 137 rows
Threshold Bit Score: 337.877
Threshold Setting Gi: 256670147
Created: 4-Aug-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
NAD(P) binding
Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:NAD(P) binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                   ##                                   
2J8Z_A        23 MLAVHFDkpggPENLYVk--eVAKPSPGe--gEVLLKVAASALNRADLMQRQGq-YDPPPGasnILGLEASGHVAELGpg 97  human
XP_844089      4 MRAVTLKaygaVNMLGIg--qVPEPAFSrp-nDVLIKVVAAGVNRADISQRRGh-YPPPPGvseLLGLEVSGVVLRVGsn 79  Trypanosoma bru...
XP_001466629   4 MRAVTLKgfgdTDMLQIs--rIPKAAITrg-rDILIKVSAAGVNRADAAQRKGh-YPPPKGsseVLGLEVSGIVEQVGdd 79  Leishmania infa...
ZP_02184373    1 MKVVSIKkpgnSKELEMqerpIPKPEMG----QLLVKVKASAINRTDIMTRENrqLPEPYP---ILGIEVAGVVVENQds 73  Carnobacterium ...
XP_002110278   1 MRSVLVGe---KGSLTIvn-dTPLPSLKt--gQILIKVAACGVNRMDLLQRYNk-YPVPVGeseILGVEVAGTIAEMDee 73  Trichoplax adha...
YP_661739      1 MQFIDYEegtaTDTLFVn--dTTKPTLKq--gQVLVKVHSFGINRADTLQRQGk-YPAPRGespILGLEVSGEIVSLGis 75  Pseudoalteromon...
YP_002126680   1 MHYVDFAkgckPDELTV----KEQAGYSltagKVKVEVKAFGVNRADTLQRQGn-YPPPPGeseILGLEVAGVVSEVAsd 75  Alteromonas mac...
YP_269965      1 MKYIHVDn---QQSLVFsqtdMPKIVAD----ECLIKVHAIGINRADLLQRAGk-YPAPAGessILGLEVSGEIVQCGda 72  Colwellia psych...
YP_339826      1 MKYISHE----DGILAFs--eTNKPVLKs--hEVLVKVAAIGVNRADCMQRQGk-YPAPKDdsqILGLECAGIVCDIGgk 71  Pseudoalteromon...
XP_645256      3 MRSILVKqfggIENLIIg--tAPKPTPKn--nEILVHVKSFALNRADILQRMGr-YPPPPGdsdILGLEMSGVVVEADkq 77  Dictyostelium d...
Feature 1                                                            #   #  #                 #  
2J8Z_A        98 c-----qghWKIGDTAMALLpGGGQAQYVTVPeGLLMPIPEgLTLTQAAAIPEAWLTAFQLLHLVGnVQAGDYVLIHAGL 172 human
XP_844089     80 v------krFGEGDRVMALLaGGGYADLVVAHeGSVMKIPDeYSFVEAAAIPEGFLTAWQLLRRHGsLKKGQCVLVHAGA 153 Trypanosoma bru...
XP_001466629  80 v------kdFKEGDKVMALLpGGGYAEYAVAHeGSVMHIPQgYSFIEAAAIPEAFLTAWQALKYHGdCRRGQKVLIHAGA 153 Leishmania infa...
ZP_02184373   74 s-----nnqLVPGTRVAGLVnHGGYAEYVVMPaDRAIRIPDnMSFEEAAAIPEVFLTAYQTLYWLGeLESEETVLIHAGA 148 Carnobacterium ...
XP_002110278  74 al---hhsnFKVGDRVCALVgGGGYADFCASPhQTVMPIPRsMSFVEASAIPEAFLTAYAAMFLSAkLKKDESILIHAGA 150 Trichoplax adha...
YP_661739     76 adn--essrWQIGDEVFALVaGGGYAQYVAVNsEHLMPKPKnVDMPSAAGIAEVFLTAYQSLFQVGgLKTGQRVLIHAGA 153 Pseudoalteromon...
YP_002126680  76 v------stFKEGDRVCGLVaGGGYATEALVNpAHLMRIPQgMPFFEAAGLTEVFLTAFQCLRTIAhIKPAQRALIHGGA 149 Alteromonas mac...
YP_269965     73 vsdnhlaqsWQVGDKVFGLVaGGGYAQYVKVKaRQLFCLPEqFTFEQGAACAEVFLTAYQSLFSIAkLANNSKVLIHAGA 152 Colwellia psych...
YP_339826     72 v------dkIWLNKRVFALCaGGAYSEYVAVDaKQLMELPDdVSMREGAAISEVYLTAFGALFELGkLQAGQTALIHAGA 145 Pseudoalteromon...
XP_645256     78 d------krFKIGDKVFGLVgGGAYGEFCTIAsNQAFHMPShLTFESASAIPEAWLTAFQALHPLAnFKSGNSVLIHAAA 151 Dictyostelium d...
Feature 1        ###                   ##   #              #                           ##        
2J8Z_A       173 SGVGTAAIQLTRMAGAi-pLVTAGSqKKLQMAEkLGAaAGFNYkk----edFSEATLkftkgaGVNLILDCIGGSy-WEK 246 human
XP_844089    154 SGVGTSLMQLAGKYFGakvVATCSE-GKVDFCK-KFAdIVVDRspdemgrcFCHKVKsavgddAVNLVVDPVVGGsyLNE 231 Trypanosoma bru...
XP_001466629 154 SGVGTAAAQLVEKYFQataLTTSSE-SKVEVCKnFAS-INLTRtpdetgmcFSPKVKsllgegAINLVLDSVFGGsyISE 231 Leishmania infa...
ZP_02184373  149 SGVGTAAIQLAKKMTKakvIVTAGStEKLQFCKeLGAdKLINYke----eeFDQLVLeyteqkGVDLILDFVGASy-WEK 223 Carnobacterium ...
XP_002110278 151 SGVGTAAIQLAKEFGNkdiFVTAGSeKKLAMCReLGAtTLINYkt----hdFAEVVRhttnkrGVDVVVDFIGASy-WER 225 Trichoplax adha...
YP_661739    154 SAVGLAAIQLAKADGCh-vSVTASTeKKLAVCEkYGAdRLINYkt----qnFAECFEq----gGVDVIIDFVAGDy-LNR 223 Pseudoalteromon...
YP_002126680 150 SGVGLAATQLCRYWGVh-sAVTASSqEKLSLCEkNGAeQLINYkq----qaFDEVLKkaw-peGVDMVLDMVGGDy-LNR 222 Alteromonas mac...
YP_269965    153 SGVGSAAIQLAKAKQCy-vTVTVGSeVKAQACLaLGAdCAINYqk----ndFVAWSKenv-laGYDVIIDVVSGEy-LSK 225 Colwellia psych...
YP_339826    146 SGVGGAAIQMAKSAGAt-vVITAGSdEKCAHAKaLGAdHAINYkt----tdFVEYMKan--nlTANTIVDPVSGSy-LNK 217 Pseudoalteromon...
XP_645256    152 SGVGTALIQLCKVDGAtkiIGTVGSdEKAKFIEkLGAtHSVNYktn---enFLDVINdvtskkGVNNVFDYVGAKy-WNQ 227 Dictyostelium d...
Feature 1                     ## #                        ###                                    
2J8Z_A       247 NVNCLalDGRWVLYGLMGGgdin--gplFSKLLfKRGSLITSLLRsrDNKYKQMLVNAFteQILPHFSTEgpqrllpVLD 324 human
XP_844089    232 DGIVLaqDGKIVVIALMGGskv---elnISTLLrKRGTIVFSKLRdqTDEYKASLVEEFerEVIPYLKDRii---tpIVQ 305 Trypanosoma bru...
XP_001466629 232 DAAVLakDGRIVVLAFMGGatv---hlnCLPLLrQRAHVMFSKLRcqSDDYKQNLVDTFeeAVIPYMNERli---vpVAN 305 Leishmania infa...
ZP_02184373  224 NLNSLktDGRWVVIGVLGGavve--nvnLGMLLqKRITLKGTLLTprSDDYKAQLTNEFieNVLPYFEKGli---kpIVD 298 Carnobacterium ...
XP_002110278 226 NIKSLalDGRLVLLGLLGNtatdgihcnTGLILaKRLTIIGSTLRnrDINYKSNLILDFtrSTVDGFQKGrl---kpVLD 302 Trichoplax adha...
YP_661739    224 NLKILnaDGTIVYLAMLAGryad--kvdMALMLaKRATITGSTLRsrSDEYKSVLIHDFchRFLADFDNGal---rpVID 298 Pseudoalteromon...
YP_002126680 223 NLQVLkrDGSVVYLAMLAGryad--nldMAMLLgKRASIIGTTLRnrSDEYKANLIGEFatACIPAFESKel---tvNID 297 Alteromonas mac...
YP_269965    226 NINVAalDGHIVTLSMLGGrycs--qvdIAKLLaKRLTLSASTLRnrSEDYKAQLVDNFssDFYADLVNGqi---kpIID 300 Colwellia psych...
YP_339826    218 NAAVAamDCQIVMLAFLDGrfa---evdFARLLqKRISFHASTLRnrSIEFKRALRDDFvaRFYSDIASKsy---nfNLY 291 Pseudoalteromon...
XP_645256    228 NLKSLsmDGVMIIQGFLSGshikdtaadITPILgKRLTIKGSTLRnrDNDYKADLVAQFskRYLTLFESGel---kpIVD 304 Dictyostelium d...
Feature 1                      #    #      
2J8Z_A       325 RIYPVTEIqeAHKYMEanKNIGKIVL 350 human
XP_844089    306 RTFAMEDVaeAHVFMEgnMTNGKVIL 331 Trypanosoma brucei TREU927
XP_001466629 306 KTYPLEEVaqAHARLDdrKAWGKIVL 331 Leishmania infantum JPCM5
ZP_02184373  299 IVFPLDEVakAHQYMEenKNSGKIIL 324 Carnobacterium sp. AT7
XP_002110278 303 STYTIEEVeaAHDRMLrnLNSGKIVL 328 Trichoplax adhaerens
YP_661739    299 TQYNVKDIalTHERLErnDTMGKLVV 324 Pseudoalteromonas atlantica T6c
YP_002126680 298 THYSIKDIdkPHGRLEnnDTQGKLVV 323 Alteromonas macleodii 'Deep ecotype'
YP_269965    301 SIYPWQQVeqAHEKMAknKNVGKLVL 326 Colwellia psychrerythraea 34H
YP_339826    292 KVLPWSQAseAHAILErnENAGKVVL 317 Pseudoalteromonas haloplanktis TAC125
XP_645256    305 KVFNVSEIkeAHEYLEanKNMGKVVV 330 Dictyostelium discoideum AX4

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