Conserved Protein Domain Family
Zn_ADH10

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cd08263: Zn_ADH10 
Alcohol dehydrogenases of the MDR family
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 have 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: 176224
View PSSM: cd08263
Aligned: 11 rows
Threshold Bit Score: 508.064
Threshold Setting Gi: 70607933
Created: 22-May-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Feature 1:putative NAD(P) binding site [chemical binding site]
Evidence:
  • Comment:MDR family binds NAD(P) as a cofactor
  • Comment:defined by comparison to MDR alcohol dehydrogenase like family

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                              ###  #                                    
ABK23280      45 MRAAVFWEp-GRPLSIEDFHMPRPKAGEVLIKTKACGVCHSDLHVMNGDLpf---aRPCVVGHEITGEVVEHGVHTEsgi 120 Sitka spruce
XP_001767634  52 MKAAVLWEp-RKAMTIEELKLPRPQVGEVLIRTKACGVCHSDLHVMNNDIpf---pIPCVLGHEVSGEVVEHGKHTDsat 127 Physcomitrella ...
NP_342005      9 MKGAILYKynEPLIIEDNIQIDEPKVGETKIRIEATGLCHSDVNVFEGKTpv---pPPVIAGHEIAGVIEEVGNNVTd-- 83  Sulfolobus solf...
NP_851257     56 MRGAVYREp-NKPLTIEEFHIPRPKSNEILIKTKACGVCHSDLHVMKGEIpf---aSPCVIGHEITGEVVEHGPLTDhki 131 thale cress
YP_001103638   1 MRAAVHTAa-NEPMRIEELADPHPRAGEIAIDVTSCGACHTDLHVLKGELpf---pVPAVLGHEVAGVVSEIGPEVTg-- 74  Saccharopolyspo...
YP_001361969  12 MLAAVLSPd-SAEFVLERVPVPAPRAGEALIRVAACGVCHSDLHVLKGEIaf---pRPAVLGHEISGTIVQLGDGVEn-- 85  Kineococcus rad...
YP_256803      1 MKAAIFKGa-NAPLQLTDIPKPSPGEGEILIRVASTGVCHSDIHHMKGELlgfmppEGFILGHEISGWVEDFGPNVTnp- 78  Sulfolobus acid...
NP_560362      7 MRAALYKAp-GQPLELAETEIPTPGEGEILIKVAATGVCHSDLHILDGEIvp--ppEGFILGHEVSGWVVDFGPRCEnp- 82  Pyrobaculum aer...
NP_343845      1 MKAAVYKGy-GLPLEIEEVPNPAPKEGEVLVKVASTGICHSDLHLLSGELvgp-lpNGFIIGHEIAGWVEKIGENVKnp- 77  Sulfolobus solf...
CAF18461       1 MEAAILEKy-NSELVIEEVDVEPPKSGEVALRVKAAGVCHSDLYVLEGATpv---pPPLVPGHEAVAEVIEVGPDVQg-- 74  Thermoproteus t...
YP_003150285  16 MLAAVWQGd-SPKLTVEEIPVPQPQEGEALVRVTACGVCHTDLHVLKGEVaf---pGPAVVGHEISGTIAQVGPGVEg-- 89  Kytococcus sede...
Feature 1                                                                                        
ABK23280     121 ikrFPIGAHVVGAFIMPCGNCFYCVKGQEDLCEPFftynrakgtlydgetRLFLrsngkpvyMYSMGGLAEYCVVPATAL 200 Sitka spruce
XP_001767634 128 ierLPVGSRVVGAFIMPCGGCFFCVKGQEDLCESFlkynrglgglydgttRLYMsssgdpvyMYSMGGLAEYCVVPANGL 207 Physcomitrella ...
NP_342005     84 ---FKPGDRVISAFIHPCGKCKNCITGKENLCEVFaknrlng-tlldgttRLHFkdgt-pirAFLGGGFAEYAMVPYTAL 158 Sulfolobus solf...
NP_851257    132 inrFPIGSRVVGAFIMPCGTCSYCAKGHDDLCEDFfaynrakgtlydgetRLFLrhddspvyMYSMGGMAEYCVTPAHGL 211 thale cress
YP_001103638  75 ---FSVGDRVVTSFIMPCGQCGQCARGNEEICEKFfaynrgkgqlydgetRLFRpgge-pvwMYSMGGLAERSVTPATAA 150 Saccharopolyspo...
YP_001361969  86 ---LRVGDAVVGGFIMPCTRCDECQRGRDDLCPQFfaqnrlkgalfdgetRLRRtdgs-plaMYSMAGLAEYSVCPVSAL 161 Kineococcus rad...
YP_256803     79 -ygLQKGDPVIVSWIVPCGKCRYCASGKENYCNNVm-------------mKMPGl-------IGINGGHAEYTSVPEIAV 137 Sulfolobus acid...
NP_560362     83 -hgLSPGDPVVISWIIPCGKCYWCVRGQENYCPYAa-------------aRMPGl-------VGLNGGHAEYMSVPETAV 141 Pyrobaculum aer...
NP_343845     78 -ygLKEGDPVLVSWIVPCGICRYCANGKENYCKDNa-------------kRLVGl-------IGINGGHAEYLTVPEIAV 136 Sulfolobus solf...
CAF18461      75 ---LSRGDLVVTSFIWPCGRCRNCARGHENLCERFsevrlkg-vlldgttRLRRrksgeplrIFLGGLWAQEAVVPASAV 150 Thermoproteus t...
YP_003150285  90 ---LATGDRVVGAFVMPCGHCRHCERGRDDMCETFfaenrlkgnlldgtsRLTRpdgs-rlsMYSMGGMAEFAVVPVTAL 165 Kytococcus sede...
Feature 1                         #   #                    ######                  ##   #        
ABK23280     201 AVLPAs-LPYTESAILGCAAFTAYGAMRHAadmrAGETVAVIGIGGVGSSCLQIAKAFGGskIIAVDVQDEKLENARKLG 279 Sitka spruce
XP_001767634 208 AVIPEs-LPYSESAIIGCAVFTAYGAMKNAadmrAGETVAVIGTGGVGSSCIQVSRAFGGriVIGVDISDGKLEMAKQMG 286 Physcomitrella ...
NP_342005    159 TKVPEd-LDLRKVAVLGCAGLTAYGAVNSAki-ePGETVAVIGVGGVGLSVIQMLKIAGAgrIIAVGTRKWKLEKALELG 236 Sulfolobus solf...
NP_851257    212 APLPEs-LPYSESAILGCAVFTAYGAMAHAaeirPGDSIAVIGIGGVGSSCLQIARAFGAsdIIAVDVQDDKLQKAKTLG 290 thale cress
YP_001103638 151 YRVPDg-VELADVASVGCSTMTAYGALRHAadvrVGDTVAVVAAGGVGSALIQLAGSFGAsvVVAVDISEDKLANARALG 229 Saccharopolyspo...
YP_001361969 162 AVLPSe-VSMTSAAVLGCAGMTAYGAVHRAgsvqPGATVAVVAVGGLGMSMVQLAAAAGAstVVAVDVNDEKLAMARRLG 240 Kineococcus rad...
YP_256803    138 IPAREi-KDVIASSPVSCAYGTAYGALKTAga-sAGQSVVVIGTGGVGSAAIQLASVMGLypIIAVDVVDSKLAKVKELG 215 Sulfolobus acid...
NP_560362    142 FPIPKe-VDVHTAAVISCAYGTAYRALKEAav-gPGTSLVVIGVGGVGLAAVELASALGArpIIAVDVRKHVLEKAAELG 219 Pyrobaculum aer...
NP_343845    137 IPLAKn-LDPYYSSPIACAYGTAYNALKSAna-tSGKSVVIVGAGGVGSAAIQLANSIGLnpIVAVDIDENKLKSAKLLG 214 Sulfolobus solf...
CAF18461     151 AKLPPrlANRPELAMLGCAFLTAYGAVVNSgsvqPGDTVAVIGTGGVGLAIVQVARAVGAr-VIAVGRNPEKLKLAAEMG 229 Thermoproteus t...
YP_003150285 166 TALDEa-LPMDSSCVLGCAGFTAYGALAASgl-qAGESMAVVAVGGVGSSIVQMGKHLGAsaVVALDVTDEKLAGARVLG 243 Kytococcus sede...
Feature 1              #                        ## #                    ##                       
ABK23280     280 AtHTVNASKVNv-vDTIKEITgGRGVDIAVEALGKpetFMQTALSVMD-GGKAVMIGLaasg-akaEIDITRLVRrQIKI 356 Sitka spruce
XP_001767634 287 AtHTINASKEDv-pERIREITgGRGVDIAVEALGKp-aTFKQAIMSVRdGGRAVMIGLapwg-ataDIEITRLVRrQIRV 363 Physcomitrella ...
NP_342005    237 AsDVVNSKETDv-vRAVKNIT-GGGPDVVIEVAGTt-eTVKMSLDMVRiGGKVVLVGLpptt-aeiPIRIASIVRgGIKI 312 Sulfolobus solf...
NP_851257    291 AtHIVNAAKEDa-vERIREITgGMGVDVAVEALGKpqtFMQCTLSVKD-GGKAVMIGLsqag-svgEIDINRLVRrKIKV 367 thale cress
YP_001103638 230 AtHTVNSAEVDa-pAAIREITgGRGVDVAFEALGSv-pTFEAARDSVVeGGQIVVVGIaprg-tsgEFDLATIARrKLQI 306 Saccharopolyspo...
YP_001361969 241 AtHTVNSAKEDa-hAAVRAATgGRGVDVAIEALGRp-aTLRLAVDVLAdGGRAVAVGLaagn-aevGIEITPFVRrSRSL 317 Kineococcus rad...
YP_256803    216 AtHTVNPNKEDp-vGKITEIL-PEGADIVYETKPNp--DLQIAFNVVNkSGTMVVTGLgnatsstiNLMTNLFVGrGLKV 291 Sulfolobus acid...
NP_560362    220 AtHLINATNGDp-lSKIRDIL-PQGADVVYETKPNp--DLKLAVEIVRrGGTIVVTGLgts---tiEIPANHIVMnGIRI 292 Pyrobaculum aer...
NP_343845    215 AtHIINANENDa-rAKVLEAL-EDGADIVYETKPYp--DFKLSLEVVKsGGTIVVTGLggfs-tlaQIPVTLFVSrGITL 289 Sulfolobus solf...
CAF18461     230 A-EVVNARDGDa-vAEVRKLTdGRGADVVVEAVGSe-qTVEQAIDMAStGGRVVLVGLmglg-kkaPLHVARVVRgGISV 305 Thermoproteus t...
YP_003150285 244 AtHTVNTAATDdpaAAVREAV-PGGVDVVFEALGRp-eTFELSQSLLAdGGRMVAVGIaagd-ataRVPITQLVRrGHTI 320 Kytococcus sede...
Feature 1          ###                                                     
ABK23280     357 LGSYGGRARqDLPILVGLAETGIFNLEaAVSKKCTFDEAGAVYDALNRGEiVGRAVVE 414 Sitka spruce
XP_001767634 364 FGSYGGRARqDLPNIVGLAEMGFLKIEsAVTQKAKLEQASNVYAELEQGRiTGRAVIE 421 Physcomitrella patens subsp. patens
NP_342005    313 IGDYGGRPRvDMPRLIELVKLGKYDPTaLVTGKFRLEEINEAVKLLEQGE-AIRSLII 369 Sulfolobus solfataricus P2
NP_851257    368 IGSYGGRARqDLPKVVKLAESGIFNLTnAVSSKYKFEDAGKAFQDLNEGKiVSRGVVE 425 thale cress
YP_001103638 307 KGSYGAKPRrDMPVLLDLVARGLLRPQdAISRRYSFDQVQDAYDALRRGEtVGRAVVD 364 Saccharopolyspora erythraea NRRL 2338
YP_001361969 318 MGSFGARTRtDLPAVVDLAARGSFDPDaLVTDVFSLEDVNEAYSRLDGGDiLGRAVVS 375 Kineococcus radiotolerans SRS30216
YP_256803    292 VGSLGYRPRiDLPELVRMVASGKLDVKkLVTHVYRPDEINTAYENLEKGL-HLRAIID 348 Sulfolobus acidocaldarius DSM 639
NP_560362    293 IGSLGYKPRtDIPELLTLAASGKIKPQrLISHKYAPNEINEAYKNLRIGL-HHRAIII 349 Pyrobaculum aerophilum str. IM2
NP_343845    290 IGSLGYRPRiDLPDLVSLASSGKIDIKkLVSHIYTPDMINEAYENLKKGL-HIRAIIR 346 Sulfolobus solfataricus P2
CAF18461     306 IGSYGARPRvDLPKVIGMVERGLLRPElMARDFYKLEQINEAVEALRSGR-SIRPIVL 362 Thermoproteus tenax
YP_003150285 321 RGSFGARTRkDLPAVVALAAEGGFDVAgAVTRTYGLDEVDRAYRDLAEGRiTGRAIVV 378 Kytococcus sedentarius DSM 20547

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