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


Conserved Protein Domain Family
liver_alcohol_DH_like

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cd08277: liver_alcohol_DH_like 
Click on image for an interactive view with Cn3D
Liver alcohol dehydrogenase
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: 176238
View PSSM: cd08277
Aligned: 14 rows
Threshold Bit Score: 489.928
Threshold Setting Gi: 2565288
Created: 30-Apr-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 22 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      7 IKCKAAVLWEekKPFSIEEVEVAPPKAhEVRIKMVATGICRSDDHVVSGtlv-tpLPVIAGHEAAGIVESIGEGVTtVRP 85  horse
1CDO_A      7 IKCKAAVAWEanKPLVIEEIEVDVPHAnEIRIKIIATGVCHTDLYHLFEgkhkdgFPVVLGHEGAGIVESVGPGVTeFQP 86  Baltic cod
1D1T_A      7 IKCKAAVLWEqkQPFSIEEIEVAPPKTkEVRIKILATGICRTDDHVIKGtmv-skFPVIVGHEATGIVESIGEGVTtVKP 85  human
1E3E_A      7 IKCKAAIAWKtgSPLCIEEIEVSPPKAcEVRIQVIATCVCPTDINATDPkkk-alFPVVLGHECAGIVESVGPGVTnFKP 85  house mouse
1MC5_A      6 IKCKAAVAWEagKPLSIEEIEVAPPKAhEVRIKIIATAVCHTDAYTLSGadpegcFPVILGHEGAGIVESVGEGVTkLKA 85  human
1QV6_A      7 IKCKAAVLWEekKPFSIEEVEVAPPKAhEVRIKMVATGICRSDDQVVSGtlv-tpLPVIAGHEAAGIVESIGEGVTtVRP 85  horse
P14674      9 IRCKAAVAWEagKPLVMEEVDVAPPQKmEVRLKILYTSLCHTDVYFWEAkgqnpvFPRILGHEAAGIVESVGEGVTeLAP 88  potato
P26325      7 IKCKAAVAWEanKPLVIEEIEVDVPHAnEIRIKIIATGVCHTDLYHLFEgkhkdgFPVVLGHEGAGIVESVGPGVTeFQP 86  Baltic cod
CAA63093    9 ITCKAAVVGKegEMIKIEEIQVDPPKSnEVRIKMLFASLCHTDILASNGypy-slFPRVLGHEGVGMIESVGENVTnLKE 87  potato
AAX83109   10 ITCKAAAAWKpsEPLVVEEICVEPPKStEVRIKMLAASMCHTDILLWKGff--plYPRIPGHEGAGVIESVGEKVAnLKV 87  sweet basil
Feature 1                                                                                     
1HET_A     86 GDKVIPLFTPQCGKCRVCKHPEGNFCLKndls----mprgTMQDGTSRFTCr-GKPIHHFlGTSTFSQYTVVDEISVAKI 160 horse
1CDO_A     87 GEKVIPLFISQCGECRFCQSPKTNQCVKgwan----espdVMSPKETRFTCk-GRKVLQFlGTSTFSQYTVVNQIAVAKI 161 Baltic cod
1D1T_A     86 GDKVIPLFLPQCRECNACRNPDGNLCIRsdit-----grgVLADGTTRFTCk-GKPVHHFlNTSTFTEYTVVDESSVAKI 159 human
1E3E_A     86 GDKVIPFFAPQCKRCKLCLSPLTNLCGKlrnfkyptidqeLMEDRTSRFTCk-GRSIYHFmGVSSFSQYTVVSEANLARV 164 house mouse
1MC5_A     86 GDTVIPLYIPQCGECKFCLNPKTNLCQKirvt----qgkgLMPDGTSRFTCk-GKTILHYmGTSTFSEYTVVADISVAKI 160 human
1QV6_A     86 GDKVIPLFTPQCGKCRVCKHPEGNFCLKndls----mprgTMQDGTSRFTCr-GKPIHHFlGTSTFSQYTVVDEISVAKI 160 horse
P14674     89 GDHVLPVFTGECKDCAHCKSEESNMCSLlrint---drgvMINDGQSRFSIn-GKPIYHFvGTSTFSEYTVVHVGCVAKI 164 potato
P26325     87 GEKVIPLFISQCGECRFCQSPKTNQCVKgwan----espdVMSPKETRFTCk-GRKVLQFlGTSTFSQYTVVNQIAVAKI 161 Baltic cod
CAA63093   88 GDIVMPLYLGECKECPNCKSGKSNLCHKyhlt-----fsgLMLDDTSRISIhgGQVLYHSfSCSTWSEYIVINANYVIKV 162 potato
AAX83109   88 GDTVMPLSIGQCGECSNCATGKTNICFKypfg-----isgLMPDGTSRMSAk-GQKLYHMfTCSTWSEYTVVDSNFVVKV 161 sweet basil
Feature 1                   #   #                    #####                   ##   #           
1HET_A    161 DAa-sPLEKVCLIGCGFSTGYGSAVKVAKVtQGSTCAVFGLGGVGLSVIMGCKAAGAaRIIGVDINKDKFAKAKEVGATE 239 horse
1CDO_A    162 DPs-aPLDTVCLLGCGVSTGFGAAVNTAKVePGSTCAVFGLGAVGLAAVMGCHSAGAkRIIAVDLNPDKFEKAKVFGATD 240 Baltic cod
1D1T_A    160 DDa-aPPEKVCLIGCGFSTGYGAAVKTGKVkPGSTCVVFGLGGVGLSVIMGCKSAGAsRIIGIDLNKDKFEKAMAVGATE 238 human
1E3E_A    165 DDe-aNLERVCLIGCGFSSGYGAAINTAKVtPGSTCAVFGLGCVGLSAIIGCKIAGAsRIIAIDINGEKFPKAKALGATD 243 house mouse
1MC5_A    161 DPl-aPLDKVCLLGCGISTGYGAAVNTAKLePGSVCAVFGLGGVGLAVIMGCKVAGAsRIIGVDINKDKFARAKEFGATE 239 human
1QV6_A    161 DAa-sPLEKVCLIGCGFSTGYGSAVKVAKVtQGSTCAVFGLGGVGLSVIMGCKAAGAaRIIGVDINKDRFAKAKEVGATE 239 horse
P14674    165 NPl-aPLDKVCVLSCGISTGLGATLNVAKPtKGSSVAIFGLGAVGLAAAEGARIAGAsRIIGVDLNASRFEQAKKFGVTE 243 potato
P26325    162 DPs-aPLDTVCLLGCGVSTGFGAAVNTAKVePGSTCAVFGLGAVGLAAVMGCHSAGAkRIIAVDLNPDKFEKAKVFGATD 240 Baltic cod
CAA63093  163 DPqkiPLQHASLLCCGFTTGYGATWREVHVeKGSTVAVLGLGVVGLGAIEGARSQGAsKIIGVDINESKQGKGELFGMTD 242 potato
AAX83109  162 DPr-iPLPHASLLTCGFLTGYGAPWRESRVeKGSTVAVIGLGAVGLGAVSASRILGAsKIIGIDVNELKREKATVFGVTE 240 sweet basil
Feature 1                                  ##   ##                 ##                         
1HET_A    240 CVNPQDYKkpiQEVLTEMSn-GGVDFSFEVIGRlDTMVTALSCCqeAYGVSVIVGVppdsqNLSMNPMLLLs---GRTWK 315 horse
1CDO_A    241 FVNPNDHSepiSQVLSKMTn-GGVDFSLECVGNvGVMRNALESClkGWGVSVLVGWtd-lhDVATRPIQLIa---GRTWK 315 Baltic cod
1D1T_A    239 CISPKDSTkpiSEVLSEMTg-NNVGYTFEVIGHlETMIDALASChmNYGTSVVVGVppsakMLTYDPMLLFt---GRTWK 314 human
1E3E_A    244 CLNPRELDkpvQDVITELTa-GGVDYSLDCAGTaQTLKAAVDCTvlGWGSCTVVGAkv--dEMTIPTVDVIl---GRSIN 317 house mouse
1MC5_A    240 CINPQDFSkpiQEVLIEMTd-GGVDYSFECIGNvKVMRAALEAChkGWGVSVVVGVaasgeEIATRPFQLVt---GRTWK 315 human
1QV6_A    240 CVNPQDYKkpiQEVLTEMSn-GGVDFSFEVIGRlDTMVTALSCCqeAYGVSVIVGVppdsqNLSMNPMLLLs---GRTWK 315 horse
P14674    244 FVNPKDYSkpvQEVIAEMTd-GGVDRSVECTGHiDAMISAFECVhdGWGVAVLVGVphkeaVFKTHPMNFLn---ERTLK 319 potato
P26325    241 FVNPNDHSepiSQVLSKMTn-GGVDFSLECVGNvGVMRNALESClkGWGVSVLVGWtd-lhDVATRPIQLIa---GRTWK 315 Baltic cod
CAA63093  243 FINPKESMtsvSEMIKDVTegLGVDYVFECTGIpSMLNEAIEASklGIGTIVVIGAg----HGLTREFNLVpllcGRTLK 318 potato
AAX83109  241 FINPKHSDktvSQLIQEATggLGVDCCIECTGVsSLLNEAIASTkvGIGEVVLIGAge-keKVEISYIPLMl---GRSVK 316 sweet basil
Feature 1      ###                                                  #    
1HET_A    316 GAIFGGFKSkdSVPKLVADFMAKKFALDpLITHVLPFEKINEGFDLLRSGE-SIRTILT 373 horse
1CDO_A    316 GSMFGGFKGkdGVPKMVKAYLDKKVKLDeFITHRMPLESVNDAIDLMKHGK-CIRTVLS 373 Baltic cod
1D1T_A    315 GCVFGGLKSrdDVPKLVTEFLAKKFDLDqLITHVLPFKKISEGFELLNSGQ-SIRTVLT 372 human
1E3E_A    318 GTFFGGWKSvdSVPNLVSDYKNKKFDLDlLVTHALPFESINDAIDLMKEGK-SIRTILT 375 house mouse
1MC5_A    316 GTAFGGWKSveSVPKLVSEYMSKKIKVDeFVTHNLSFDEINKAFELMHSGK-SIRTVVK 373 human
1QV6_A    316 GAIFGGFKSkdSVPKLVADFMAKKFALDpLITHVLPFEKINEGFDLLRSGE-SIRTILT 373 horse
P14674    320 GTFFGNYKPrsDIPSVVEKYMNKELELEkFITHTLPFAEINKAFDLMLKGE-GLRCIIT 377 potato
P26325    316 GSMFGGFKGkdGVPKMVKAYLDKKVKLDeFITHRMPLESVNDAIDLMKHGK-CIRTVLS 373 Baltic cod
CAA63093  319 GSIYGGIRLhsDLPAILHRCATKEIQLNeLITHQISLTEINQSFELLKDPH-CVKIIIK 376 potato
AAX83109  317 GTTLGGVRIhsDLPKIVEKCINKEIDLDeLITHEVSLVDVNKGFMEYMNQPdCVKVSVK 375 sweet basil

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