Conserved Protein Domain Family
liver_ADH_like1

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cd08281: liver_ADH_like1 
Zinc-dependent alcohol dehydrogenases (ADH) and class III ADG (AKA formaldehyde dehydrogenase)
NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes or ketones. This group contains members identified as zinc dependent alcohol dehydrogenases (ADH), and class III ADG (aka formaldehyde dehydrogenase, FDH). 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. 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. Class III ADH are also know as glutathione-dependent formaldehyde dehydrogenase (FDH), which convert aldehydes to the corresponding carboxylic acid and alcohol. 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: 176241
View PSSM: cd08281
Aligned: 10 rows
Threshold Bit Score: 506.53
Threshold Setting Gi: 116669881
Created: 4-May-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Feature 1:NAD binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                      ###  #                            
EDX80816       5 TRAAVLSAmga-ahPYRDSRPLSIETVTLDPPGPGEVLVAIRAAGLCHSDLSVINGDRPRPLPMALGHEAAGVVEALGDS 83  Brevundimonas s...
YP_001561214   3 TRAAVLTRtga-aaPYADSRPLEIWEVDLAPPGPGEVLVKVAAAGVCHSDLSIINGDRPRDTPIVLGHEAAGVIQALGEG 81  Delftia acidovo...
NP_693723      3 VKTAVLRTqga-dsPYKESKPIKIETLELDAPQLGEVLIQIKAASLCHSDLSVINGSRPRPLPMALGHEASGVVVEVGEG 81  Oceanobacillus ...
NP_659929      3 MRSVILREsgl-pkPYSNSKPLKIELVELTPPGPMEVLVKIKAAGVCHSDLSAINGDRPRPLPVALGHEASGVVAAIGPS 81  Rhizobium etli ...
AAL54109       3 FKAAVLDRhgv-erPYNQTKPLVIREVELREPKADEVLVKLAASGLCHSDLSVINGDRSRQIPMVLGHEAAGVVEKIGEG 81  Brucella melite...
AAZ93608       3 MKAAVLFEqgl-paPYAISQPIQIEEVELDGPGEGEVLIEVVAAGLCHSDLSTIENLRPRKVPTVIGHEAAGIVREVGAG 81  Paracoccus pant...
YP_998043      3 IRSAVLHEmna-atPFAQTRPLRIEELELDEPGPGQVLVKMVAAGLCHSDLSVITGVRPRPLPLALGHEASARVVRTGAG 81  Verminephrobact...
YP_001103782   3 VRAAVLREsga-ekPYGTSQPIDVTTLQLDPPGPGELLVRVRAAGLCHSDLSVINGSRPRPLPLALGHEAAGEVLEAEQG 81  Saccharopolyspo...
YP_830814      1 MRAAVLYAtvpagtSYTEARPLVVQELDRPEPRAGELGVAITYSSLCHSDLSVVDGSRVRPLPMALGHEAVGRVVSVGEG 80  Arthrobacter sp...
YP_002762412   5 IRAAVLRTtal-prPYGDSRPLHIESVRLSAPQEQEVRVRIAAAGLCHSDLSVVDGNRPRPLPMVLGHEAAGEVIEVGAG 83  Gemmatimonas au...
Feature 1                                                                                        
EDX80816      84 VTDlAVGDHVVMVFMPSCGHCDPCAGGRPALCEPGAaangkGELLSGARRLFREGEPVNHH-LGCSAFAERAVVSRRSLV 162 Brevundimonas s...
YP_001561214  82 VTDlEVGDHVVMLFVPGCGNCQPCAEGRPVLCEPAGqagvaGTLLSGARRLSRNGQPISHF-VGVSAFAEHAVLSRRGVH 160 Delftia acidovo...
NP_693723     82 VTYlEPGDHIVCVFVPSCGHCVPCKEGRPALCEPGAdsntaGTLISGGIRLHADGEAINHH-LGVSAFSEFAVVSRNSLV 160 Oceanobacillus ...
NP_659929     82 VEKvEVGDHVVMSFLPVCGHCSYCAEGRASLCEPGYqanaaGTLLSGGKHIRLRGYEINHH-SGVSAFSEYAVVSASSVV 160 Rhizobium etli ...
AAL54109      82 VTDlVPGDHVVCVFVPNCGHCQPCAEGRPALCEPGAaangkGEMLSGGLRLFCDDGDVYHH-CGVSAYAEYAVMSRYSII 160 Brucella melite...
AAZ93608      82 VRRlKVGDHVVATFVASCGCCRYCIDHRANLCTASWtsraeGTLQSGARRLKFGKGDLHHY-TGLSTFAEYAVVSESSLV 160 Paracoccus pant...
YP_998043     82 VTDlRAGDLVVLIFVPSCGHCMPCMQGRPALCEPAAeangnGTLFGGDKRLRLRNTAVYHH-TGVSAFSDHAVVSRQSCV 160 Verminephrobact...
YP_001103782  82 SGF-EPGDHVVLAFVPSCGECERCVAGRPALCGPAAaantkGALLGGGMRFTEEDGSRPYHhLGVSAFAEHIVVSSRSAV 160 Saccharopolyspo...
YP_830814     81 VHDvAVGEHVVLVFVPSCGDCRACRSGRPALCHRAAevnasGDLLHGAALLRTPSGERINHhLGVSAFADYAVVARESVV 160 Arthrobacter sp...
YP_002762412  84 VRDlMVGDHVVFSFVPQCGHCAPCRSARPALCEPGAaangaGELLDGGRRLRDMNDTPMHHhLGVSGFAEEVVVSRQSVV 163 Gemmatimonas au...
Feature 1                       #   #                    #####                   ##   #          
EDX80816     163 KIDPDLSFEEAALFGCAVLTGVGAVVNTAGVKAGQSVVVIGLGGVGLSSVLGALASGAsPVVAVDLSEDKLALARTLGAT 242 Brevundimonas s...
YP_001561214 161 RIDKSVPLELAALFGCAVMTGVGAVANTARVSPGQSVAVVGLGGVGLSSVMGAAAAGAaRVVAVDLNADKLAMAREFGAT 240 Delftia acidovo...
NP_693723    161 KVKKDIPFEKLALFGCAVITGVGAVVNTANVKLGSTVAIVGLGGIGLSALLGAVAAGAsRIIAVDINENKLKQAKELGAT 240 Oceanobacillus ...
NP_659929    161 KVTKDIDLATAALFGCAVMTGVGAVMNTCGVRPGRSVAVIGLGGVGLSAILGAVASGAsDIVAIDLIQAKLDLAKELGAT 240 Rhizobium etli ...
AAL54109     161 RIEKDIPLHIAALMGCAVLTGTGSIFNTGLVKPGSRVAIAGLGGVGLAAVMGAVAAGAtEIIALDMFDDKLALAEQLGAT 240 Brucella melite...
AAZ93608     161 SIRKDVPLEVAALFGCAVVTGVGAVFNTAALRPGQSAAVVGLGGVGLNALLGAVAAGAyPVIAIDMNPEKLELAKSLGAS 240 Paracoccus pant...
YP_998043    161 KVDADIDPVQAAMFGCAVLTGVGAVINTAGAQAGSTAALVGLGGVGLCALLAAVASGCrQVVAVDIHDSKLALARSLGAS 240 Verminephrobact...
YP_001103782 161 KVDPEVPFEIAALFGCAVLTGAGAALYSAQIRPGDSVAVFGLGGVGLAALLAAKAAGAsTVVAVDVVEHKRKLASELGAT 240 Saccharopolyspo...
YP_830814    161 VIDDDVPDTVAAMFGCAVLTGMGAVLNTAAVTAGQSVAVFGLGAVGLSAVMAASLAGAaAIIAIDPNEGKHQLARDCGAT 240 Arthrobacter sp...
YP_002762412 164 RVDRSLPFEIGALFGCAVMTGVGAIVNTAKLRLGESVLITGLGGIGFAALLGALASGAgQVVVADVSDDKLQQALALGAH 243 Gemmatimonas au...
Feature 1                                       ###   #                ###                       
EDX80816     243 sglvQTVNGADpdavdQVRALTNGGADFAFEMAGSaRALDTAWKMTRRGGTTVTAGLPpPEAALAVNIVSLVGEERTLKG 322 Brevundimonas s...
YP_001561214 241 ----DIVNAGDedavkQVRELTGGGVDHAFEMVGSaKALEMAYRITRRGGQTVTAGLPsSAQAISLPVWHLVAEERTLKG 316 Delftia acidovo...
NP_693723    241 ----DVFNSTEetviqQIKEATDGGVNYAFETAGAvPAMEVAYGITKRGGTTVTTGLPhPEHQFSFPYVTLTAEEKTLKG 316 Oceanobacillus ...
NP_659929    241 ----KTFLATSpnivaQVKGATSGGVDYAIEMAGSkKAFELAYEITRRGGMTATAGLAsANSRFEVSPLPLVGEERTIKG 316 Rhizobium etli ...
AAL54109     241 ----KTFNVQSegvveAVKEYTKGGVDAAFEYAGSgAALAMCYALTKRGGEVVTAGLPnPKNMLSIPAVSLVAEEKSIRG 316 Brucella melite...
AAZ93608     241 ----HAVLASDpnmaeQVKDLTNGGVDFAFEAAGSiPAVHTAYQCLARGGTVISSGLPdPTKTYAYNHAPLVSDEKSIRG 316 Paracoccus pant...
YP_998043    241 ----AAVNARDpdaveQIRALTHGGVDYSFEMAGSvPSMETAYSITRRGGMTVTAGLPaPTDRWPLRQLSLVVEERTVKG 316 Verminephrobact...
YP_001103782 241 ----HTVEGGPda-vqRVRELTSGGAEKVLDTTGVvHVLQQAYDATRSGGTTVTVGLPdPEARLTLPALSIVAEERTLRG 315 Saccharopolyspo...
YP_830814    241 ----AVGTPDDaa--rLVAEATGDGVDVAVEAVGSaGVIASCLELVTRGGAVVSVGLPkPSAELTVGALQFAGAGKRLLG 314 Arthrobacter sp...
YP_002762412 244 ----AAVNSGAdnaleRVRGLTGGGADVGLECAGVvAALDFTWRGTRRGGRTVTVGLPhPSQTLSISPVQLVAEERTLQG 319 Gemmatimonas au...
Feature 1        ###                                          #      #    
EDX80816     323 SYIGTCVPsRDILRYVALYRQGRLPVDRLMSGVIPLDDINAGFDRLHAGEVVRLVVR 379 Brevundimonas sp. BAL3
YP_001561214 317 CYMGSCVPrRDIDRYLALHAAGRLPVDRLVTGHLTLDQINEGFDRLARGEAIRQIIR 373 Delftia acidovorans SPH-1
NP_693723    317 SYVGSCVPdRDIPRYMNLFKQDRLPVDKLMTDFISLDEINEGFDKLAKGDSSRIIIK 373 Oceanobacillus iheyensis HTE831
NP_659929    317 SYMGSCVPsRDIPRYIDLYLKGKLPVDKLLSSTGPLDEINEVFDRLDRAEINRHLVL 373 Rhizobium etli CFN 42
AAL54109     317 SYLGSGVPtRDIPLFLDLYRKGKLPVEKLLTHRIKLEEINEGFERLAAGKAIRQVVE 373 Brucella melitensis 16M
AAZ93608     317 SYMGGCDPrRDVPRYLNLYLAGKLPVDRLRSGDLTFEQINQGFDALALGKVVRQTLR 373 Paracoccus pantotrophus
YP_998043    317 SYIGSCVPvRDVPRYIAMYLGGQLPIDRLMGQRHPLDDINAGFDRLNSGESLRDVIV 373 Verminephrobacter eiseniae EF01-2
YP_001103782 316 SYLGSCVPrRDVPRFIQMYQSGALPVDALLSHRLGLDEINAGFDRLDDGTAVRQVVL 372 Saccharopolyspora erythraea NRRL 2338
YP_830814    315 SYMGDAVPeREIPLYLDYWRSGRLPVELLHTDTRPLAEINEGLDALAAGQVVRRLFQ 371 Arthrobacter sp. FB24
YP_002762412 320 SYLGSCVPsRDIPAYIALYQSGRLPVDKLLTHRLSLDEINDGFDRLARGEAIRQVIL 376 Gemmatimonas aurantiaca T-27

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