Conserved Protein Domain Family
Zn_ADH6

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cd08260: Zn_ADH6 
Alcohol dehydrogenases of the MDR family
NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. This group has the characteristic catalytic and structural zinc sites of the zinc-dependent alcohol dehydrogenases. 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: 176221
View PSSM: cd08260
Aligned: 27 rows
Threshold Bit Score: 463.997
Threshold Setting Gi: 229822141
Created: 13-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                                             ###  #                                     
YP_002784931   1 MKAVMVHAFNVRPELVTVSDPTPPEDGVVVQVGATGVCRSDWHGWVGHDPd----ITLPHVPGHELAGTVVAVGKNIRrW 76  Deinococcus des...
YP_134960      1 MQAVLLEEFQEPLTVQEVERPEPEPDGAVAEVIGCGICRSDWHCWQGDWDwfgyrPDPPHVLGHEPTGRIVSVGEDVEnI 80  Haloarcula mari...
ZP_04000482    1 MDAVVFQGVDEPLELRSVDRPDCDANGVVVETEACGICRSDWHAWQGDWEwlgiiPQPGLIFGHEPVGRIVEVGENVTrF 80  Halogeometricum...
YP_055250      1 MKAALVEQYHEPLAIRDIPEPAHDSDGVVVEVKACGVCRSDWHGWQGEWPgf-tgGSLPHIFGHEFVGLVSDIGNNVSrY 79  Propionibacteri...
YP_136721      1 MRAAVLEAYGEPLAVRDRDPPTPNPDGAVVAVEACGICRSDWHAWQGHGDwadddVPIGQVLGHEPAGRVTATGNQVTtV 80  Haloarcula mari...
YP_511906      1 MRAAVVRDFNADLALERVPDPACPETGVVLEVAACGVCRSDYHGWTGGHPn----VVNGSILGHEYCGTVVEAGPRAQ-H 75  Jannaschia sp. ...
YP_167126      1 MRAAQLTAWRQPLTLATLPDPTPGPGEVVLRVLACGVCRSDWHAWTGADPd----VELPLVPGHEFCGEVVALGTGVSrW 76  Silicibacter po...
YP_002566457   1 MRAAILREYGEPLDIHEVPDPEPGPDGAVVRVTACGVCRSDWHAWAGHGEwaddrVPRGQVLGHEPAGEVVTVGDSVDrF 80  Halorubrum lacu...
YP_002949021   1 MKAAKIIQHKKPLEILNVPDPKPGPEDAVIKIEACGVCRSDWHAWQGDWSwiglsPELPITPGHEFGGVIEEVGKDVKsF 80  Geobacillus sp....
YP_326290      1 MRAVVFEEAGEPMEVQEVDRPEADADEIVVETEACGVCRSDWHAWQGDWDwigvaPTPGLVFGHEPVGTVKEVGEDVSeL 80  Natronomonas ph...
Feature 1                                                                                 #   #  
YP_002784931  77 KVGDRVTVPFVSGCGRCHECQSGNQQVCDRQFQPGFTh--WGSFAEYVALhQAEQNLVALPDDLDFVTAASLGCRFATSF 154 Deinococcus des...
YP_134960     81 EEGQEVAIPFNFACGNCDLCRNGRENICENHIGLGFMnqaPGAFAEEVHIpNADLNAVPLPDDIDAESAAGMGCRFMTSF 160 Haloarcula mari...
ZP_04000482   81 SEGEMVTNPFNLSDGTCPYCRAGRGNICESSIPMGFVhfqKGAFAEEYSVrNADQNLIKVPEDVPAREIAGLGCRFATAF 160 Halogeometricum...
YP_055250     80 RVGDRVIVPFTLGCGHCEYCRSGHSNVCPTVSMPGFSy--DGGFAQYVTVpDADANLVKLPDAVDFTDAAGMGCRLMTAY 157 Propionibacteri...
YP_136721     81 SVGDRVVVPFNLGDGTCGYCRNGHGNVCTDGWALGFEsdaPGAFAEQVAVpQADYNLVGLPDGVSSDAAAALGCRYVTAF 160 Haloarcula mari...
YP_511906     76 KVGDRLIAPFILGCGACPACQTGASNTCAHQVVPGFGa--PGAYAECVAV-PFDHNLVHLPDSLSPALAAGLGCRVTTAW 152 Jannaschia sp. ...
YP_167126     77 RLGDRVIAPFILACGRCGDCAAGHQTICANQQVPGFTr--NGAFAELIAVpFADTNLTALPDSLPPHVAAGLGCRVTTAW 154 Silicibacter po...
YP_002566457  81 APGDRVVVPFSLGDGTCPRCRQGHGNVCDDGRALGFEpeaPGAFAERVAVpDADYNLVERPPWLDATAAAALGCRYMTAY 160 Halorubrum lacu...
YP_002949021  81 RPGDRVTVPFHSACGRCEYCKKGVPNLCENLQIYGLVsglEGGYAEYVLVrNADFNLIRLPENVDSLTAAALGCRYMTGY 160 Geobacillus sp....
YP_326290     81 SVGDRVCVPFNLSDGTCRYCKQGRANICERVVPMGFVpfqPGAFAEEFPVrNADHNAIKIPDGVDPVDVAGLGCRFATAF 160 Natronomonas ph...
Feature 1                          ######                 ##   #              #                  
YP_002784931 155 RAVVHQGRVrAGEWVAVHGCGGVGLSAIMIAKALGAGVVAVDIDEEKLRFAGQLGAdLLINSRa--tPDVAGAVRDLTGG 232 Deinococcus des...
YP_134960    161 HAMAHRAPVsAGDDVVIHGCGGIGLSAVHIANALGGNVIGVDLMDEKLDRAEELGAvATVNAQe--vDDPAKAVRDITDG 238 Haloarcula mari...
ZP_04000482  161 HGVSQRVDIkAGDWVAVHGCGGVGLSAVHTATALGGNVIAIDIVEEKLEFARDLGAvETINSTe--vDDIPQAVKSITDG 238 Halogeometricum...
YP_055250    158 HGIVEVGQIhPGDWLVVYGAGGVGLSATLVATSAGANVIAVDIADDKLALARKVGAiATINSRe---TDPVEAVRELTDG 234 Propionibacteri...
YP_136721    161 HALAHRADIaAGDRVAVHGCGGLGLAAVQIASALGASVIAVDIRDEPLAMARDAGAsTVVDASa--vEDVPAAIEGETDG 238 Haloarcula mari...
YP_511906    153 QALTDRADVkAGEWVAVHGTGGIGLSVLLLAKMLGARVVVVDIVDEKLEHAVTHGAdATVNASq---VDAAAAIRDITGG 229 Jannaschia sp. ...
YP_167126    155 QALVGRAELrPGEWLAVFGGGGVGLSALLLGRALGARVVVVDVVEDKLTHAKSLGAdAVVNAAd---TDAAEAVRELTGG 231 Silicibacter po...
YP_002566457 161 HALAERAGLdGGEWLAVHGCGGVGLSAVQLGDALGARIVAVDVDDDALSLARDLGAdETVNPNdldeETVPDRVRNLTDG 240 Halorubrum lacu...
YP_002949021 161 HGIVRGNVK-PGDWVAVHGAGGVGLSAIQVANALGAQVIAVDIDDQKLEIAKQEGAiAVVNARk---ENVVEAIKEITKG 236 Geobacillus sp....
YP_326290    161 HGLVHRVDVtPGDWVAVHGCGGVGLSAIHVADALGANVIGVDLGEDKLDKAVELGAdATVNVTe--vEDVPQAVKAHTPS 238 Natronomonas ph...
Feature 1                 ## #                   ##                          ###                 
YP_002784931 233 --GVHVSLDALGHpeTCANSVANLRTRGRHVQVGLLLAEQsr-pAIPMDRVIArELELYGSHGMAAHAYPEMLAMISRGA 309 Deinococcus des...
YP_134960    239 --GADVSADALGIatTCQNAVNSLRKGGTHVQIGLTTSEEagmvSLPTDEFVAkEIDFKGSLGLQPSRYSEMLDMVESSK 316 Haloarcula mari...
ZP_04000482  239 grGVSVSVEALGIsqTIKDSVNCLAPGGQHLQVGLTTSEEggevSLPIDFMVQdEREFYGTYGMPPHEYDDIFRMMSSGK 318 Halogeometricum...
YP_055250    235 --GADKSVDALGIseTLHNAVNSLRSRGTHIQIGMTAEGPvgdvALTINDLIAkEIDFRGSFGMPAVEFRYLLNQVAAGK 312 Propionibacteri...
YP_136721    239 --GAEVSVDALGRaeTCQNSVRSLRPRGTHVQVGLTTNAErgevALPTDWITRwDIDVLGSRGMPPSRYDELLRLVADGP 316 Haloarcula mari...
YP_511906    230 --GAHVSIEALGIaaTTNASVECLATLGRHVHVGMPAGDGm--mEINMRAIYAkQLAFYGTRGMPSWKYPTLLGMIERGD 305 Jannaschia sp. ...
YP_167126    232 --GAHVAVEALGIaaTMTGAMRSLRKLGRLVMIGMPAGEHta-mTLPMDVLYSgQLTLQGTRGMPAWRYPSLLSLIDGGH 308 Silicibacter po...
YP_002566457 241 --GADVSVDALGIaeTCRNSVRSVRPRGTHVQVGLTTEAErgevSLPTDWMTRwEVSFVGSRGMPPTSYDDLFALVEATD 318 Halorubrum lacu...
YP_002949021 237 --GAHVGLDALGIkdTVLNSVLSLRKGGRHVQVGLTTSEEggfvSLPVDLITAsEIEFVGSIGNPHPDYRGLLSLISSGR 314 Geobacillus sp....
YP_326290    239 srGVEVSVDALGVaeTCRNSVNSLAKGGQNLQIGLTTSEEegevSLPVDNIVMeEREFVGSFGMPPHEYEEIFSMMAQDK 318 Natronomonas ph...
Feature 1                                            
YP_002784931 310 LRPDqLLGQRVTLEQSIDVLVNMDRFVERGVTVIDR 345 Deinococcus deserti VCD115
YP_134960    317 LDPTaLVEDTVDIHQVPDELAAMSDYNTVGIPVCNE 352 Haloarcula marismortui ATCC 43049
ZP_04000482  319 IDPGkIVSETCSLGDIPSVMERLGEYDTMGIPVCTE 354 Halogeometricum borinquense DSM 11551
YP_055250    313 MKPGqLVTKTIALSEVNDALTAMSTYNTVGTTVITD 348 Propionibacterium acnes KPA171202
YP_136721    317 LDPGaLVTRRVALEAVSERLAAMTDYGTDGIELVTE 352 Haloarcula marismortui ATCC 43049
YP_511906    306 VDISpMVAREIPLSAASAELRAMGGPTPPGTAVITD 341 Jannaschia sp. CCS1
YP_167126    309 VDLSpLVTRTIALSQASDELAAFDRPAPPGVAVITD 344 Silicibacter pomeroyi DSS-3
YP_002566457 319 VDPAaLVSEELALSEVSERLAAMGEYDARGVEVVTD 354 Halorubrum lacusprofundi ATCC 49239
YP_002949021 315 LNPKrLVEREIKLEDVNAVFENMSQYNTKGFNVITK 350 Geobacillus sp. WCH70
YP_326290    319 IDPGkIVSETVSLEEVPEVIASMDDYGTVGIPVCDE 354 Natronomonas pharaonis DSM 2160

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