2EIH,2EIH


Conserved Protein Domain Family
Zn_ADH_like1

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cd08266: Zn_ADH_like1 
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Alcohol dehydrogenases of the MDR family
This group contains proteins related to the zinc-dependent alcohol dehydrogenases. However, while the group has structural zinc site characteristic of these enzymes, it lacks the consensus site for a catalytic zinc. 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. 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 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: 176227
View PSSM: cd08266
Aligned: 18 rows
Threshold Bit Score: 452.096
Threshold Setting Gi: 13471258
Created: 24-Jul-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
putative NAD(P)structural Zn
Conserved site includes 24 residues -Click on image for an interactive view with Cn3D
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                                                       ###  #                           
2EIH_A         1 MRAVVMRar----gGPEVLEVADl---PVPEPg-pKEVRVRLKAAALNHLDVWVRKGvaspklpLPHVLGADGSGVVDAV 72  Thermus thermop...
AAC07327       1 MKAVILTgf----gGIENLKYVEd--fPKPEPk-eDEVLIRVKAVALNHLDIWVRMGalpvkpeLPHILGSDVSGVVEKV 73  Aquifex aeolicu...
NP_102827      1 MRALQLI-------EDRRLETVDl---PPPPPpalGEVTLRIRAVALNHIDVWGWRGmafakrkLPLVVGAEASGEVEAV 70  Mesorhizobium l...
AAM12917       1 MRALQLV-------DKQRLALRElvlpARPAP---GHARVRMAFMTLNHLDLFGYRGmafarrtLPVTVGAEGAGFVQDV 70  Pseudomonas flu...
YP_591720      1 MKAIRIHgf----gGPEVLKYEDv---PEPELr-kDQVLVQVKACALNHLDLFVRKGipg--ikPPLILGSDVSGVVAKV 70  Acidobacteria b...
YP_823714      1 MKVARIHqh----gGPEVLVYEDv---PEPKIk-aNQVLIRVRACALNHLDLFVRAGipgmkfsMPHVLGSDIAGEVVEV 72  Solibacter usit...
YP_876666      1 MKAVVYEeyapdddYKKILRVKDid-ePKPRA---DEVIFTVKAAALNYNDIWGMRGqpv-pvpLPHVSGSDAAGDVTAV 75  Cenarchaeum sym...
YP_001543118   2 MKAGFFRhh----gGLEVLEYGDl---AEPVAg-pDEVLVRVRAAALNHLDLFVREGlpglnlpMPHIGGCDIAGEIAAI 73  Herpetosiphon a...
YP_001736798   1 MRAVVIRkh----gGPEVLEFEEd--yPDPKIg-pNDVLVEVKAVAMNHLDIWVRKGvrg--atLPRILGSDISGIVKEV 71  Candidatus Kora...
YP_001931282   1 MKAAYYDkl----eGYKAIKIGDf---PIPEIn-dDEVLVNIKAFSLNHLDVWVMEGkypmpipLPHIFASDGAGIVAKT 72  Sulfurihydrogen...
Feature 1                                                                                        
2EIH_A        73 GpgvegfaPGDEVVinpGLSCGRCERCLAGEDNLCp-rYQILGEHRHGt---YAEYVVLPEANLAPKPKnLSFEEAAAIP 148 Thermus thermop...
AAC07327      74 GslvknvkEGEEVIiapGLSCGVCWDCQSGRDNHCk-dYDILGLKNKGg---YAEYVAVPARNVIKKPKnLSFEEAASYP 149 Aquifex aeolicu...
NP_102827     71 GpgvssllPGQLVSiygARTCGLCRACREGRDNLCehvSGVHGFHLDGf---AQEKINLPARLLVPAPPgVSDIGAAVAP 147 Mesorhizobium l...
AAM12917      71 GpgsdpelIGQAMAiypSVFCGCCPACLAGRENLCadsPGVMGFHCDGv---AAEYVDVPLRMLVPIPAgVPMDMAACAP 147 Pseudomonas flu...
YP_591720     71 EeyitdlkEGQRVLlapMRACYHCEFCLRGEHSFCa-qFAVRGTRFDGg---DCEYVAVPRVEVIPIPEsLTYDEAASVP 146 Acidobacteria b...
YP_823714     73 GelcervkPGWRVLlapGVSCRQCEQCLSGKDNFCr-kFTNLGYGVDGg---NTELLAVSEYSVIQIPDdMSFEDAAAAP 148 Solibacter usit...
YP_876666     76 GedvkdikIGDRVVshsNMSCRICSACTDGREFDCi-kRTIWGFQTGPnwgaFQESTHLPEVNVSRIPEgVSYEHAAAAS 154 Cenarchaeum sym...
YP_001543118  74 GegvtgwrEGQRVVvnpNIWCGACEYCIAGEETLCd-rYGVIGEHQTGg---LAQYIAVPARNLYAIPAdYAFEQAAAVP 149 Herpetosiphon a...
YP_001736798  72 GsgvsdvkVGEEVIvspGYGCGKCEYCLSGRESMCk-qYKMPGYHVDGg---YAELTSHPERAILRKPAnLNFEEAASVP 147 Candidatus Kora...
YP_001931282  73 GknvknvkEGDRVVifsGLSCGYCEKCLSGRDNECn-qFRPLGVLEDGv---SAEYVKVPAVNVFKIPDdFSFEEASCLP 148 Sulfurihydrogen...
Feature 1        #   #                    #### ##                 ##   #              #          
2EIH_A       149 LTFLTAWQMVVdKLGVRPGDDVLVMAAGSGVSVAAIQIAKLFGARVIATAGSeDKLRRAKALGADETVNYthp----dwP 224 Thermus thermop...
AAC07327     150 LTFLTVWNALVdKAQIKPYSRVFIWAGSSGVGVAGIQLAKAFNAFVITTAGNeEKAKKCKELGADLVFNHyk-----ddV 224 Aquifex aeolicu...
NP_102827    148 VTFGTVEHMLFdNARLQPGETILVHAGGSGIGSAAIQLAKRMGCTIITTVGSnDKIDKAKALGADHVINYred----rfE 223 Mesorhizobium l...
AAM12917     148 VTFATVHHMLIdNARLMSGETLLVHAGGSGIGSIAIRLARHLGVTVFATVGRaDKVERARALGAEYVIDYree----rfL 223 Pseudomonas flu...
YP_591720    147 LVFLTAWHMLVsRAKIKHGQTVLVWGAGSGVGTAAIQICKLMGCTVITTAGGeRKLDLAWELGADYTIDHyk-----qkV 221 Acidobacteria b...
YP_823714    149 LVFLTAWHMLMsRARLQAGEDVLVLSASSGVGTAAIQIAKLFHCRVIATAGNeQKLAKARELGADHVIDHyqq----diS 224 Solibacter usit...
YP_876666    155 MTILTSWHMLVgRARIRPGQTVLIMGGGSGVGSFGIQIAKLYNCDVIATASP-DKLDKCKELGADYAVDHrkedwhkevR 233 Cenarchaeum sym...
YP_001543118 150 LVWMTAWRALIgQAQLRAGQSVLILGAGGGVASAAIQIARYAGATVYAASRSpEKLARAQELGADYVVRSdg-----dwG 224 Herpetosiphon a...
YP_001736798 148 LVFLTSWHMLRtLADVREDEWVLIWGAGSGVGISSIQIAKLLGAKVIATVGDdWKVERAYKIGADHVINRkk-----edV 222 Candidatus Kora...
YP_001931282 149 ITYITMWHSLItRTKIKAGDIVLIHGGASGVGTAGIQLAKLFGATVITTVGDdWKVEKCKNLGADYVINYkne----dfV 224 Sulfurihydrogen...
Feature 1                             ## #                  ##                       ###         
2EIH_A       225 KEVRRLtg----gkGADKVVDHTGAlyFEGVIKATAnGGRIAIAGASSGYegtlPFAHVFYRQLSILGSTMaskSRLFPI 300 Thermus thermop...
AAC07327     225 VKKVREvf----keGVDVVVDHIGEatFWKSVQMLRkGGKLVFFGTTTGSkgeiDIRYVFVREIQLLGVYMgsrANLFKI 300 Aquifex aeolicu...
NP_102827    224 GVVRKLtk----kkGVDVVFEHVGAdtFAGSMLCLKrGGRLVTCGSTSGVstqiNLMQLFQQQLKLLGSFGcrmENMANA 299 Mesorhizobium l...
AAM12917     224 RVIREQta----rrGVDVVFEHVGAdtWEQSLLSLArGGRLVICGSTTGVeaptNLMHLFNQQIHIHGSFGaplSGLRDA 299 Pseudomonas flu...
YP_591720    222 SDEVKKiv----kgGVDVVFEHTGEktWPESLRSMRvGGTLVTCGATTGPeaklDLRVLFTRQLTFMGSFMgtfDDLNEA 297 Acidobacteria b...
YP_823714    225 AEVRKFtg----krGVDVVVEHVGLatWQKSLESLAlGGRLITCGATTGYdarvDLRFLFSKQWSLLGSFMgtlGELHQV 300 Solibacter usit...
YP_876666    234 AITKEIakrkgeapGIDVSFDHIGQthWNKQLTLLKyGATLVSCGATTGYdaktDLRHIFFKGTNILGSTQgtkAELDQA 313 Cenarchaeum sym...
YP_001543118 225 RELWKQtn----krGVDVVLENVGAatWESSLRSVAkGGTVVTYGATTGPivniDIRKLFWRQFNLIGSTMannREFNTI 300 Herpetosiphon a...
YP_001736798 223 IARVKElt----geGVDVVVDSVGSetWMSSLKCLRvGGRMVSVGATSGEqasiDVRYIFSRQLRILGSYMgsrAELIEV 298 Candidatus Kora...
YP_001931282 225 EKVKEIts----nnLCDVVIDHIGAetFNKSLSCAKkGGNVITFGSTTGAevniNLRYVFGKNLTIHGVYMgtkGEFSHV 300 Sulfurihydrogen...
Feature 1                                                    
2EIH_A       301 LRFVEegk-lkPVVGQVLPLEAAAEG-HRLLEeRRVFGKVVLQV 342 Thermus thermophilus HB8
AAC07327     301 TELFErgv-fkPVVDKVFPLKEVPQA-HKYLEeSKHFGKVVLKV 342 Aquifex aeolicus VF5
NP_102827    300 MQKMAagq-vaPVIDTEVGFDDIDAA-LKRMEgRDVFGKIILRV 341 Mesorhizobium loti MAFF303099
AAM12917     300 LALIQqg--vlPVIDCVMPVAGFESG-LQRLReRDVFGKIVLQF 340 Pseudomonas fluorescens
YP_591720    298 LKYVFsga-lkPVVDRSFALREAAAA-HSYLEkGEQFGKVVLNP 339 Acidobacteria bacterium Ellin345
YP_823714    301 LKFVFrkq-lhPVIDRAFPLSGIAEA-HRYLEnKEQFGKVILTV 342 Solibacter usitatus Ellin6076
YP_876666    314 LYWMGqgk-ikAAIDSTYSFGQAAEAhAKMLSgKGLFGKILMKP 356 Cenarchaeum symbiosum A
YP_001543118 301 MRLVFwerrfqPLIDKVFPLSEIQAA-QRYLEsAEQFGKVVITI 343 Herpetosiphon aurantiacus ATCC 23779
YP_001736798 299 LKFFErgk-lrPVIDSVFKLEEARKA-HERMEgSEMFGKIVILP 340 Candidatus Korarchaeum cryptofilum OPF8
YP_001931282 301 LKLIPnk--irPVIDSVFELEDIQKA-YEKLLsRQFFGKIVVKI 341 Sulfurihydrogenibium sp. YO3AOP1

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