1D1T,1E3E,1E3I,1EE2,1HDX,1HDZ,1HET,1HSO,1HT0,1HTB,1JU9,1P0C,1QV6,3COS,6ADH


Conserved Protein Domain Family
alcohol_DH_class_I_II_IV

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cd08299: alcohol_DH_class_I_II_IV 
Click on image for an interactive view with Cn3D
class I, II, IV alcohol dehydrogenases
NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes or ketones. This group includes alcohol dehydrogenases corresponding to mammalian classes I, II, IV. 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 (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.
Statistics
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PSSM-Id: 176259
View PSSM: cd08299
Aligned: 55 rows
Threshold Bit Score: 645.523
Threshold Setting Gi: 6647422
Created: 24-Dec-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                                                  ##                                 
1D1T_A      2 TAGKVIKCKAAVLWEqKQPFSIEEIEVAPPKTkEVRIKILATGICRTDDHVIKGtm-vsKFPVIVGHEATGIVESIGEGV 80  human
1E3E_A      2 TQGKVIKCKAAIAWKtGSPLCIEEIEVSPPKAcEVRIQVIATCVCPTDINATDPkk-kaLFPVVLGHECAGIVESVGPGV 80  house mouse
1E3I_A      2 TQGKVIKCKAAIAWKtGSPLCIEEIEVSPPKAcEVRIQVIATCVCPTDINATDPkk-kaLFPVVLGHECAGIVESVGPGV 80  house mouse
3COS_A      4 TKGKVIKCKAAIAWEaGKPLCIEEVEVAPPKAhEVRIQIIATSLCHTDATVIDSkfeglAFPVIVGHEAAGIVESIGPGV 83  human
O46649      3 TKGKVIKCKAAIAWEaGKPLSIEEVEVAPPKAhEVRVQINAAGLCRSDTHVINPkfegaFLPVILGHEGAGIVESVGPGV 82  rabbit
O46650      3 TKGKVIKCKAAIAWEaGKPLSIEEVEVAPPKAhEVRVQIIAASVCRSDTYVINPafkegLLPVILGHECAGIVESVGPGV 82  rabbit
Q64563      3 TQGKVITCKAAIAWKtDSPLCIEEIEVSPPKAhEVRIKVIATCVCPTDINATNPkk-kaLFPVVLGHECAGIVESVGPGV 81  Norway rat
Q9QYY9      3 TQGKVIKCKAAIAWKtGSPLCIEEIEVSPPKAcEVRIQVIATCVCPTDINATDPkk-kaLFPVVLGHECAGIVESVGPGV 81  house mouse
Q5R7Z8      3 TTGQVIRCKAAILWKpGAPFSIEEVEVAPPKAkEVRIKVVATGLCGTEMKVLGSkhldlLYPTILGHEGAGIVESIGEGV 82  Sumatran orangutan
P08319      3 TKGKVIKCKAAIAWEaGKPLCIEEVEVAPPKAhEVRIQIIATSLCHTDATVIDSkfeglAFPVIVGHEAAGIVESIGPGV 82  human
Feature 1                                                                                     
1D1T_A     81 TTVKPGDKVIPLFLPQCRECNACRNPDGNLCIRSDITg-----rGVLADGTTRFTCkGKPVHHFLNTSTFTEYTVVDESS 155 human
1E3E_A     81 TNFKPGDKVIPFFAPQCKRCKLCLSPLTNLCGKLRNFkyptidqELMEDRTSRFTCkGRSIYHFMGVSSFSQYTVVSEAN 160 house mouse
1E3I_A     81 TNFKPGDKVIPFFAPQCKRCKLCLSPLTNLCGKLRNFkyptidqELMEDRTSRFTCkGRSIYHFMGVSSFSQYTVVSEAN 160 house mouse
3COS_A     84 TNVKPGDKVIPLYAPLCRKCKFCLSPLTNLCGKISNLkspasdqQLMEDKTSRFTCkGKPVYHFFGTSTFSQYTVVSDIN 163 human
O46649     83 TNVKPGDKVIPLYIPHCKKCKFCLSPLTNFCEKFCKGknplieqELMEDKTSRFTCkGKSIYHFFGISAFSQYTVVKDVN 162 rabbit
O46650     83 NNFKPGDKVIPLYVPHCRKCKFCQSPLTNFCTKFSEHknpiieqELMDDKTSRFTCkGKSIYHFLGISAFSQYTVVKDIN 162 rabbit
Q64563     82 TNFKPGDKVIPFFAPQCKKCKLCLSPLTNLCGKLRNFkyptidqELMEDRTSRFTSkERSIYHFMGVSSFSQYTVVSEAN 161 Norway rat
Q9QYY9     82 TNFKPGDKVIPFFAPQCKRCKLCLSPLTNLCGKLRNFkyptidqELMEDRTSRFTCkGRSIYHFMGVSSFSQYTVVSEAN 161 house mouse
Q5R7Z8     83 STVKPGDKVITLFLPQCGECTSCLNSEGNFCIQFKQSe-----tQLMSDGTSRFTCkGKSIYHFGNTSTFCEYTVIKEIS 157 Sumatran orangutan
P08319     83 TNVKPGDKVIPLYAPLCRKCKFCLSPLTNLCGKISNLkspasdqQLMEDKTSRFTCkGKPVYHFFGTSTFSQYTVVSDIN 162 human
Feature 1                      #   #                    #####                   ##   #        
1D1T_A    156 VAKIDDaaPPEKVCLIGCGFSTGYGAAVKTGKVKPGSTCVVFGLGGVGLSVIMGCKSAGASRIIGIDLNKDKFEKAMAVG 235 human
1E3E_A    161 LARVDDeaNLERVCLIGCGFSSGYGAAINTAKVTPGSTCAVFGLGCVGLSAIIGCKIAGASRIIAIDINGEKFPKAKALG 240 house mouse
1E3I_A    161 LARVDDeaNLERVCLIGCGFSSGYGAAINTAKVTPGSTCAVFGLGCVGLSAIIGCKIAGASRIIAIDINGEKFPKAKALG 240 house mouse
3COS_A    164 LAKIDDdaNLERVCLLGCGFSTGYGAAINNAKVTPGSTCAVFGLGGVGLSAVMGCKAAGASRIIGIDINSEKFVKAKALG 243 human
O46649    163 LAKIDDdaNLERVCLIGCGFSTGYGAAINTAKVTPGSTCAVFGLGGVGLSAIMGCKTAGASRIIAIDINSDKFAKAKALG 242 rabbit
O46650    163 LAKIDDdaNLKRVCLIGCGFSTGYGAAINDAKVTPGSTCAVFGLGGVGLSAVIGCKTAGASRIIAVDINSDKFAKAKALG 242 rabbit
Q64563    162 LARVDDeaNLERVCLIGCGFTSGYGAAINTAKVTPGSACAVFGLGCVGLSAVIGCKIAGASRIIAIDINSEKFPKAKALG 241 Norway rat
Q9QYY9    162 LARVDDeaNLERVCLIGCGFSSGYGAAINTAKVTPGSTCAVFGLGCVGLSAIIGCKIAGASRIIAIDINGEKFPKAKALG 241 house mouse
Q5R7Z8    158 VAKIDAvaPLEKVCLISCGFSTGFGAAINTAKVTPGSTCAVFGLGGVGSSVVMGCKAAGATRIIGVDVNKEKFKKARELG 237 Sumatran orangutan
P08319    163 LAKIDDdaNLERVCLLGCGFSTGYGAAINNAKVTPGSTCAVFGLGGVGLSAVMGCKAAGASRIIGIDINSEKFVKAKALG 242 human
Feature 1                                    ##   ##                 ##                       
1D1T_A    236 ATECISPKDSTKPISEVLSEMTgNNVGYTFEVIGHLETMIDALASCHmNYGTSVVVGVPPsakMLTYDPMLLFTGRTWKG 315 human
1E3E_A    241 ATDCLNPRELDKPVQDVITELTaGGVDYSLDCAGTAQTLKAAVDCTVlGWGSCTVVGAKVd--EMTIPTVDVILGRSING 318 house mouse
1E3I_A    241 ATDCLNPRELDKPVQDVITELTaGGVDYSLDCAGTAQTLKAAVDCTVlGWGSCTVVGAKVd--EMTIPTVDVILGRSING 318 house mouse
3COS_A    244 ATDCLNPRDLHKPIQEVIIELTkGGVDFALDCAGGSETMKAALDCTTaGWGSCTFIGVAAgskGLTVFPEELIIGRTING 323 human
O46649    243 ATDCLNPRELNKPVQDVIVEMTnGGVDFAIDCAGGSEVMKATVDCATvGWGSCTFVGVNLadkGLTISPIELILGRTLKG 322 rabbit
O46650    243 ATDCLNPRELNKPVQDVIVEMTnGGVDFAIDCAGGSEVMKATVDCTTvGWGSCTFVGVNVndkGLTISPVELILGRTLRG 322 rabbit
Q64563    242 ATDCLNPRDLDKPVQDVITELTgGGVDFSLDCAGTAQTLKAAVDCTVvGWGSCTVVGAKVd--EMNISTVDMILGRSVKG 319 Norway rat
Q9QYY9    242 ATDCLNPRELDKPVQDVITELTaGGVDYSLDCAGTAQTLKAAVDCTVlGWGSCTVVGAKVd--EMTIPTVDVILGRSING 319 house mouse
Q5R7Z8    238 ATECLNPQDLKKPIQEVLFDMTdAGIDFCFEAIGNLDVLAAALASCNeSYGVCVVVGLLPasvQLKISGQLFFSGRSLKG 317 Sumatran orangutan
P08319    243 ATDCLNPRDLHKPIQEVIIELTkGGVDFALDCAGGSETMKAALDCTTaGWGSCTFIGVAAgskGLTVFPEELIIGRTING 322 human
Feature 1     ###                                                 #     
1D1T_A    316 CVFGGLKSrdDVPKLVTEFLAKKFDLDqLITHVLPFKKISEGFELLNSGQSIRTVLTF 373 human
1E3E_A    319 TFFGGWKSvdSVPNLVSDYKNKKFDLDlLVTHALPFESINDAIDLMKEGKSIRTILTF 376 house mouse
1E3I_A    319 TFFGGWKSvdSVPNLVSDYKNKKFDLDlLVTHALPFESINDAIDLMKEGKSIRTILTF 376 house mouse
3COS_A    324 TFFGGWKSvdSIPKLVTDYKNKKFNLDaLVTHTLPFDKISEAFDLMNQGKSIRTILIF 381 human
O46649    323 TNFGGWDAe-TVPKLVSDYKNGKFDLDaLVTHTLPFDKINEALNLLDQGKSIRTVLIF 379 rabbit
O46650    323 SSFGGWDVd-TVPKLVSDYKNGKFNLEaLVTHTLPFEKINEALDLLKQGKSIRTILIY 379 rabbit
Q64563    320 TFFGGWKSvdSVPNLVTDYKNKKFDLDlLVTHALPFDKINDAIDLMNQGKSIRTILTF 377 Norway rat
Q9QYY9    320 TFFGGWKSvdSVPNLVSDYKNKKFDLDlLVTHALPFESINDAIDLMKEGKSIRTILTF 377 house mouse
Q5R7Z8    318 SVFGGWKSrqHIPKLVADYMAKKLNLDpLITHTLNLDKINEAVELMKTGKCIRCILLL 375 Sumatran orangutan
P08319    323 TFFGGWKSvdSIPKLVTDYKNKKFNLDaLVTHTLPFDKISEAFDLMNQGKSIRTILIF 380 human

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