1HET,1D1T,1E3E,1E3I,1F8F,1MC5,1QV6


Conserved Protein Domain Family
Zn_ADH1

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cd05279: Zn_ADH1 
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Liver alcohol dehydrogenase and related zinc-dependent alcohol dehydrogenases
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. There are 7 vertebrate ADH 7 classes, 6 of which have been identified in humans. Class III, glutathione-dependent formaldehyde dehydrogenase, has been identified as the primordial form and exists in diverse species, including plants, micro-organisms, vertebrates, and invertebrates. Class I, typified by liver dehydrogenase, is an evolving form. Gene duplication and functional specialization of ADH into ADH classes and subclasses created numerous forms in vertebrates. For example, the A, B and C (formerly alpha, beta, gamma) human class I subunits have high overall structural similarity, but differ in the substrate binding pocket and therefore in substrate specificity. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine (His-51), the ribose of NAD, a serine (Ser-48), 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. 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 an 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.
Statistics
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PSSM-Id: 176182
View PSSM: cd05279
Aligned: 9 rows
Threshold Bit Score: 495.421
Threshold Setting Gi: 196185840
Created: 26-Jul-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 24 residues -Click on image for an interactive view with Cn3D
Feature 1:NAD binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                     ###  #                             
1HET_A         9 CKAAVLWEek--------kPFSIEEVEVAPPKahEVRIKMVATGICRSDDHVVSgtlv-tplPVIAGHEAAGIVESIGEG 79  horse
1D1T_A         9 CKAAVLWEqk--------qPFSIEEIEVAPPKtkEVRIKILATGICRTDDHVIKgtmv-skfPVIVGHEATGIVESIGEG 79  human
1E3E_A         9 CKAAIAWKtg--------sPLCIEEIEVSPPKacEVRIQVIATCVCPTDINATDpkkk-alfPVVLGHECAGIVESVGPG 79  house mouse
1E3I_A         9 CKAAIAWKtg--------sPLCIEEIEVSPPKacEVRIQVIATCVCPTDINATDpkkk-alfPVVLGHECAGIVESVGPG 79  house mouse
1F8F_A         7 IIAAVTPCkg--------aDFELQALKIRQPQgdEVLVKVVATGMCHTDLIVRDqkyp-vplPAVLGHEGSGIIEAIGPN 77  Acinetobacter c...
1MC5_A         8 CKAAVAWEag--------kPLSIEEIEVAPPKahEVRIKIIATAVCHTDAYTLSgadpegcfPVILGHEGAGIVESVGEG 79  human
1QV6_A         9 CKAAVLWEek--------kPFSIEEVEVAPPKahEVRIKMVATGICRSDDQVVSgtlv-tplPVIAGHEAAGIVESIGEG 79  horse
EDX80816       5 TRAAVLSAmgaahpyrdsrPLSIETVTLDPPGpgEVLVAIRAAGLCHSDLSVINgdrp-rplPMALGHEAAGVVEALGDS 83  Brevundimonas s...
YP_002521996   3 ARAAVLAEvk--------kPLEIWELEVDAPKegEVLVRVVAAGVCHSDLHYIQgdle-tplPAIPGHEGAGVVEAVGPG 73  Thermomicrobium...
Feature 1                                                                                        
1HET_A        80 VTtvRPGDKVIPLFtpqCGKCRVCkhPEGNFClkndlsm----prgtmqDGTSRFTCr--GKPIHHFlGTSTFSQYTVVd 153 horse
1D1T_A        80 VTtvKPGDKVIPLFlpqCRECNACrnPDGNLCirsdit-----grgvlaDGTTRFTCk--GKPVHHFlNTSTFTEYTVVd 152 human
1E3E_A        80 VTnfKPGDKVIPFFapqCKRCKLClsPLTNLCgklrnfkyptidqelmeDRTSRFTCk--GRSIYHFmGVSSFSQYTVVs 157 house mouse
1E3I_A        80 VTnfKPGDKVIPFFapqCKRCKLClsPLTNLCgklrnfkyptidqelmeDRTSRFTCk--GRSIYHFmGVSSFSQYTVVs 157 house mouse
1F8F_A        78 VTelQVGDHVVLSYg-yCGKCTQCntGNPAYCseffgrn----fsgadsEGNHALCThdqGVVNDHFfAQSSFATYALSr 152 Acinetobacter c...
1MC5_A        80 VTklKAGDTVIPLYipqCGECKFClnPKTNLCqkirvtq----gkglmpDGTSRFTCk--GKTILHYmGTSTFSEYTVVa 153 human
1QV6_A        80 VTtvRPGDKVIPLFtpqCGKCRVCkhPEGNFClkndlsm----prgtmqDGTSRFTCr--GKPIHHFlGTSTFSQYTVVd 153 horse
EDX80816      84 VTdlAVGDHVVMVFmpsCGHCDPCagGRPALCepgaaan----gkgellSGARRLFRe--GEPVNHHlGCSAFAERAVVs 157 Brevundimonas s...
YP_002521996  74 VTrfRPGDPVVFVFrafCGHCFYClnGRPALCdfsnpir----rtgrmfDGTTRFHRn--GTDVHHVlGVSCFAEYTVVp 147 Thermomicrobium...
Feature 1                            #   #                    #####                   ##   #     
1HET_A       154 EISVAKIDAasPLEKVCLIGCGFSTGYGSAVKVAKVtqGSTCAVFGLGGVGLSVIMGCKAAGAaRIIGVDINKDKFAKAK 233 horse
1D1T_A       153 ESSVAKIDDaaPPEKVCLIGCGFSTGYGAAVKTGKVkpGSTCVVFGLGGVGLSVIMGCKSAGAsRIIGIDLNKDKFEKAM 232 human
1E3E_A       158 EANLARVDDeaNLERVCLIGCGFSSGYGAAINTAKVtpGSTCAVFGLGCVGLSAIIGCKIAGAsRIIAIDINGEKFPKAK 237 house mouse
1E3I_A       158 EANLARVDDeaNLERVCLIGCGFSSGYGAAINTAKVtpGSTCAVFGLGCVGLSAIIGCKIAGAsRIIAIDINGEKFPKAK 237 house mouse
1F8F_A       153 ENNTVKVTKdvPIELLGPLGCGIQTGAGACINALKVtpASSFVTWGAGAVGLSALLAAKVCGAsIIIAVDIVESRLELAK 232 Acinetobacter c...
1MC5_A       154 DISVAKIDPlaPLDKVCLLGCGISTGYGAAVNTAKLepGSVCAVFGLGGVGLAVIMGCKVAGAsRIIGVDINKDKFARAK 233 human
1QV6_A       154 EISVAKIDAasPLEKVCLIGCGFSTGYGSAVKVAKVtqGSTCAVFGLGGVGLSVIMGCKAAGAaRIIGVDINKDRFAKAK 233 horse
EDX80816     158 RRSLVKIDPdlSFEEAALFGCAVLTGVGAVVNTAGVkaGQSVVVIGLGGVGLSSVLGALASGAsPVVAVDLSEDKLALAR 237 Brevundimonas s...
YP_002521996 148 EQGLLSLPPdiPLDRAALVGCGVTTGVGAVLFAAGVraGETVLVIGCGGVGLNVVQGAALVGAgPVIAADVVPQKLEWAR 227 Thermomicrobium...
Feature 1                                                ##    #                 ###             
1HET_A       234 EVGAT----ECVNPqdyk-kpiQEVLTEms-nGGVDFSFEVIGRlDTMVTALSCCqeaYGVSVIVGVppdsqnLSMNPMl 307 horse
1D1T_A       233 AVGAT----ECISPkdst-kpiSEVLSEmt-gNNVGYTFEVIGHlETMIDALASChmnYGTSVVVGVppsakmLTYDPMl 306 human
1E3E_A       238 ALGAT----DCLNPreld-kpvQDVITElt-aGGVDYSLDCAGTaQTLKAAVDCTvlgWGSCTVVGAkv--deMTIPTVd 309 house mouse
1E3I_A       238 ALGAT----DCLNPreld-kpvQDVITElt-aGGVDYSLDCAGTaQTLKAAVDCTvlgWGSCTVVGAkv--deMTIPTVd 309 house mouse
1F8F_A       233 QLGAT----HVINSktq---dpVAAIKEit-dGGVNFALESTGSpEILKQGVDALg-iLGKIAVVGApqlgttAQFDVNd 303 Acinetobacter c...
1MC5_A       234 EFGAT----ECINPqdfs-kpiQEVLIEmt-dGGVDYSFECIGNvKVMRAALEAChkgWGVSVVVGVaasgeeIATRPFq 307 human
1QV6_A       234 EVGAT----ECVNPqdyk-kpiQEVLTEms-nGGVDFSFEVIGRlDTMVTALSCCqeaYGVSVIVGVppdsqnLSMNPMl 307 horse
EDX80816     238 TLGATsglvQTVNGadpdavdqVRALTN----GGADFAFEMAGSaRALDTAWKMTr-rGGTTVTAGLpp--peAALAVNi 310 Brevundimonas s...
YP_002521996 228 QLGAT----HTIDPreq---dvVEVVREltggRGADYAFEVIGRaDTIQQAYAATr-kGGTTVIVGLtpmgttVPLDPLd 299 Thermomicrobium...
Feature 1                    ###                                                 #    
1HET_A       308 l---lsGRTWKGAIFGgfkskdSVPKLVADFmaKKFALDpLITHVLPFEkINEGFDLLRSGesIRTILT 373 horse
1D1T_A       307 l---ftGRTWKGCVFGglksrdDVPKLVTEFlaKKFDLDqLITHVLPFKkISEGFELLNSGqsIRTVLT 372 human
1E3E_A       310 v---ilGRSINGTFFGgwksvdSVPNLVSDYknKKFDLDlLVTHALPFEsINDAIDLMKEGksIRTILT 375 house mouse
1E3I_A       310 v---ilGRSINGTFFGgwksvdSVPNLVSDYknKKFDLDlLVTHALPFEsINDAIDLMKEGksIRTILT 375 house mouse
1F8F_A       304 ll--lgGKTILGVVEGsgspkkFIPELVRLYqqGKFPFD-QLVKFYAFDeINQAAIDSRKGitLKPIIK 369 Acinetobacter calcoaceticus
1MC5_A       308 l---vtGRTWKGTAFGgwksveSVPKLVSEYmsKKIKVDeFVTHNLSFDeINKAFELMHSGksIRTVVK 373 human
1QV6_A       308 l---lsGRTWKGAIFGgfkskdSVPKLVADFmaKKFALDpLITHVLPFEkINEGFDLLRSGesIRTILT 373 horse
EDX80816     311 vslvgeERTLKGSYIGtcvpsrDILRYVALYrqGRLPVDrLMSGVIPLDdINAGFDRLHAGevVRLVVR 379 Brevundimonas sp. BAL3
YP_002521996 300 ll--rtEKTIKATLYGsanlprDIPRLLELYrlGRLRLDeLISRRLRLEeINDGFEAMLAGsvARSIVV 366 Thermomicrobium roseum DSM...

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