Conserved Protein Domain Family
Zn_ADH5

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cd08259: Zn_ADH5 
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 contains proteins that share the characteristic catalytic and structural zinc-binding sites of the zinc-dependent alcohol dehydrogenase family. 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: 176220
View PSSM: cd08259
Aligned: 15 rows
Threshold Bit Score: 388.983
Threshold Setting Gi: 15899588
Created: 25-Sep-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                                                  ###  #                                
NP_342271      1 MKAVVVPg---kQKGYRIEEvsdPIPGKd--EVVIRVNRAALCYRDLLQLQGfYPRMKYPVILGHEVVGtieqigenakg 75  Sulfolobus solf...
YP_023535      1 MKAALLYk---nEKKLRIEDv--PVPEInddEVLIKVKAAGICHTELHFIDNvLNAGKYPIIPGHEVAGivykkgknvkd 75  Picrophilus tor...
YP_002871817   1 MKAIVLKaf-ggPEQLQVEEv--PTPQVgagEVLVQVAAAGVCHHDLLHRAGrLPGAHTGVVLGHEVAGevvevgagvhh 77  Pseudomonas flu...
YP_001541428   1 MKSIIVTg----KGRFEVADsprPDPGVg--EVLIRVKYAALCYRDLLQLRGyYPRMKYPVVLGHEAVGvveesr--dsr 72  Caldivirga maqu...
YP_001190499   1 MRAFAAVle-rfSEPLVLRE---ADVGE---GLPVKVKASGMCGRDLVIWRGgFRNLTPPLILGHEIYGe---------- 63  Metallosphaera ...
NP_559637      1 MKAYVLRn----FKELVLSEvdrPKPGPg--RAVVKIVAAGVCYRDFLGWQG-FQRVKLPLIAGHEFAGvveevgegvse 73  Pyrobaculum aer...
NP_344193      1 MKAAILTq---fNSPFIIGN---AEPHGv--GVRINVAYTGICGRDLVIWKGgFKNLKLPLILGHEIVGy---------- 62  Sulfolobus solf...
NP_559935      1 MRAVQLIkfgapQEALQYTElpdPTPGPg--EVLVKIEAAGVCGRDLVVRKGaFPHVKPPIIPGHEGVGkvidvgagver 78  Pyrobaculum aer...
YP_001541532   1 MRAARFHe---sGKPLTIEEvpkPAPGPg--EVIVKVMAAGVCHTELHFIDGvLNLGVAPITLGHEIAGivdeigpgvss 75  Caldivirga maqu...
YP_001380245   1 MRAIRYHg---pRKPLQLEQiatPAPGPg--DVLVRVSAAGVCHTELHFLSGlLDLGVAPLTLGHEIVGrveavgegvpr 75  Anaeromyxobacte...
Feature 1                                                                               #   #    
NP_342271     76 fkEGDKVIsllyapDGTCHYCQMGEEAYChsr-vgySEELDGFFAEKAKVKVTSIVKVGTnvpdegAVLVPCVTGMVYRS 154 Sulfolobus solf...
YP_023535     76 ldLNDKVLlyyyrgCGKCDFCINGQENLCtnpemeyGFINDGGFSEYIKARETDLVKLNDdidiysIAPIACSISTGIHA 155 Picrophilus tor...
YP_002871817  78 ltVGARVVvyqrrfCGQCRDCLRGRQDLCral-glpSVDTEGAYAEYLRVPAISAIELPDgldyipAALASCPIGTSVRA 156 Pseudomonas flu...
YP_001541428  73 fkPGDRVVpilhsvDGVCDMCLRGEEAYCrsr-lsfGEEVDGFFAEYAKVTGNSLVKVPDwvsdelAALTPCVLAMIHKG 151 Caldivirga maqu...
YP_001190499  64 -yEGNPVGvygvetCGECRYCRAGKENLCena-rflGEARPGGYAEVVTVKEGGIFPLPDrey-ekYAAGVCPLATAIHS 140 Metallosphaera ...
NP_559637     74 fkPGDAVAgmmyeyCGECEYCKSGREYLCknr-kiyGEDLPGAFAEYISVDQKSLVKIPPgvsfeaASYAACVLSTVVRG 152 Pyrobaculum aer...
NP_344193     63 -yNGRPVAvypnlyCGSCDYCKSGKENLCdnarilgEGEITGGYAEQVIVPERNLIPLPDdkl-ekYAATMDPVATAIHA 140 Sulfolobus solf...
NP_559935     79 dlIGMRVFlsa-iyDGTCDYCRRGFENLCrna-ellGEMRNGTYGEYVVIPAKFAHPFHGvdp-kaAVLATCPISTAVYV 155 Pyrobaculum aer...
YP_001541532  76 vkPGDRVIvyyyvgCGRCRFCLRGEENLCenikaeyGFITDGGFAEYVKVPERNLVKLPSnltfeeAAPIGCSVTTAIHA 155 Caldivirga maqu...
YP_001380245  76 erVGERVIlyyyagCGRCPHCLRGDENLCdalraehGFVTDGGFAEYVRVPARNAVPLPDaigdaeAAPIGCGVTTAVHA 155 Anaeromyxobacte...
Feature 1                        #### ##                 ##   #               #                  
NP_342271    155 LRr-AKLQKGetVLVTGASGGVGIHAIQVAKAlGAKVIGVTTSe-EKAAFIr-kFADHVIVGsk--fSEEAKkig----- 224 Sulfolobus solf...
YP_023535    156 LNm-AKPELNd-RVLVYGVGGVGFGLIQLNKLrGCRVFSASRNd-KKLDIAkklGSDYNINTcneniVNKVKsmg----- 227 Picrophilus tor...
YP_002871817 157 LHgeAALKPGesVLINGASGGLGAHQIQLAKAvGARVIAVTGSa-DKRDFLhslGADDVIVSsg-sySAEVWkltgk--- 231 Pseudomonas flu...
YP_001541428 152 LRr-IGLSIGetVLVTGAGGGVGVHAVQLAKAmGARVIAVTSHe-DKAKVLg-rFADDVIVGlk--fSEEVKrklg---- 222 Caldivirga maqu...
YP_001190499 141 SKv-AGVKKGdtVLVTGAGGGVGIHTIQYLKSlGARVVSVTSP--SKSEIVs-rFSDQVITQkd--fSKQVKdv------ 208 Metallosphaera ...
NP_559637    153 ARk-IGVSPGrqILVTGAGGGVGVHAVQVVKAyGARVIAVTSP--SKAEYVa-kFADYVITNka--fSDEVKklg----- 221 Pyrobaculum aer...
NP_344193    141 SKl-ADLKKDskVLVTGAGGGVGIHLVQYLKYlGISNVYGLSSkgEKLKEL---GVTPVSDIr----GEKFD-------- 204 Sulfolobus solf...
NP_559935    156 LK--HIDVERk-KVLVVGAGGTGIYIAQLAKVrGAEVYVSTRSp-EKASVLkelGLGVATEG-----EKDFD-------- 218 Pyrobaculum aer...
YP_001541532 156 TRr-ASPNVGd-YVVVYGVGAVGFALIQYNKMiGANVIAVGRSp-SKLKLAkelGADYTINAg----EEDVVkrvieltn 228 Caldivirga maqu...
YP_001380245 156 ANl-AGVGLGd-WVVVFGVGAVGYGLVQVARLrGARVIAVGRTp-EKLERAralGAEATVRAg----VEDVAarlreltg 228 Anaeromyxobacte...
Feature 1                 ## #                   ##                        ###                   
NP_342271    225 --dvnVVIDTVGTPt-IDESLKSLwmGGRLVQIGNVDPTQIyqLRLGYVILKdiAIIGHASATKRDAEETLKLTgEGKIN 301 Sulfolobus solf...
YP_023535    228 --gvdIIYDLVGSNetIKNDIEMLnkAGKLVLIGYDGSNVN--INPLDLIINeiKIISCVGNTRYELEEAVRLFnENRIK 303 Picrophilus tor...
YP_002871817 232 -rgvdVAMENLGST--LEDTLRSMalGGRVVVLGNVTPVSVp-INPGLLIGRrlRVQGSGSATLEEVRLALALIkGGQVK 307 Pseudomonas flu...
YP_001541428 223 -egvdAVIETVGTPt-INESLRSLriGGRILLVGNVNPDESysLRLGYVILKdvAIVSNIASNKRDVASVFNMVkSIKIE 300 Caldivirga maqu...
YP_001190499 209 ----dVVIELVGSEt-INESLRALrrEGTLVLVGNVTGKEIslARPALTIMRehRIVGSASYTRAEVEEAVKLIhEGEVK 283 Metallosphaera ...
NP_559637    222 --gadGAIEAVGGPt-LEQTLRSLnwGAKVALIGNVDPQPAp-IPLGILILKeiDVLPVIQGSKADLQEALRLLaSGAVK 297 Pyrobaculum aer...
NP_344193    205 -----AIFELVGSKt-INDSLRALkkEGILVLIGNTEGEPItlSRPAMSIMRqhKIVGSASYTQAEYEEAIKLVgYGKIK 278 Sulfolobus solf...
NP_559935    219 -----VVIDTVGAPt-LERSLKLAkrAGAVVVIGNVTGEKAl-LSPALVILRqlRVIGSMAFRPWDIYEALDLLkRGLIK 291 Pyrobaculum aer...
YP_001541532 229 grgadVVYELVGIRetMNNSVRMLakRGRLVLIGYWRDKLE--VNPLDLVIKeaTITASVGNTLSELIEAVKLVsEGKIK 306 Caldivirga maqu...
YP_001380245 229 grgadVVFELVATRetMAASSRALakRGRLVFVGYSEDTFE--IHPIQLVVGeqVVTASVGNTLAELQAAVELVaAGRVK 306 Anaeromyxobacte...
Feature 1                                       
NP_342271    302 PVIaatVGLDEIdKGYEILKDKHKIGKVLVK 332 Sulfolobus solfataricus P2
YP_023535    304 IVIdrfDELKNInNDLEIIRNGEAMGRIVIK 334 Picrophilus torridus DSM 9790
YP_002871817 308 PLIdrvLPFHQVaEAHALLESRQVNGRIVLS 338 Pseudomonas fluorescens SBW25
YP_001541428 301 PVVaakYSLQDFgRALEALQSGSRVGKILLT 331 Caldivirga maquilingensis IC-167
YP_001190499 284 PVYr-kYHLREVnTAMKDLMEGKVLGRAVLV 313 Metallosphaera sedula DSM 5348
NP_559637    298 PVYt-vHGFSDIpRLLEETPKASHVGRRVVK 327 Pyrobaculum aerophilum str. IM2
NP_344193    279 AIYe-iYELERInEAYRKMLERKVLGRAILK 308 Sulfolobus solfataricus P2
NP_559935    292 PLYv-eYKLQDAaKAHEDMERGRVMGRAVLL 321 Pyrobaculum aerophilum str. IM2
YP_001541532 307 IKVdevVGLESInDALEKLRMGKVIGRIIIN 337 Caldivirga maquilingensis IC-167
YP_001380245 307 TVVdrvLPLERFqEGIDALAAGRLVGRAVLA 337 Anaeromyxobacter sp. Fw109-5

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