Conserved Protein Domain Family
Zn_ADH_like2

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cd08264: Zn_ADH_like2 
Alcohol dehydrogenases of the MDR family
This group resembles the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase family. However, this subgroup does not contain the characteristic catalytic zinc site. Also, it contains an atypical structural zinc-binding pattern: DxxCxxCxxxxxxxC. 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: 176225
View PSSM: cd08264
Aligned: 12 rows
Threshold Bit Score: 465.288
Threshold Setting Gi: 48477918
Created: 1-May-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
putative NAD(P)putative
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                                              ###  #                                    
YP_001541497   1 MRAVVFEKSDLNDLRVVELsrpkpnphEVVIRVTESGVNPVDYYTVt---sRWVKPIPH-IPGAEFAGIVEEVGehvsvv 76  Caldivirga maqu...
NP_560184      1 MRAAAFSTPGLENLKLVEAetprpgpgEVLIRVKYAGVNPLDYNVVag--aVKASPMPH-IPGSEFAGVVEEAGpgvtgv 77  Pyrobaculum aer...
NP_394771      2 KAALVYEPLGNENLRIEDVddpkvldgQVLIEVRKAGLNPVDYNTIngkivYKLNPLPH-IPGTEVYGVVAQDSgn---f 77  Thermoplasma ac...
EAY56072       1 MKALVFDQPGIENLKITEVktpkaekgQVLIKVKMAGVNPIDALVIt---aIPSKPMPH-IPGGEFAGTVEEVGdgvtsl 76  Leptospirillum ...
YP_001190539   1 MRALVFEKRGIDFLEVRDFpsspvrddEVRLRVKLASINPVDLMAIe---sLPVSPLPH-IPGSEFYGVVEEVGekvthv 76  Metallosphaera ...
NP_343697      8 MKALVFDKSGLENLKVKEVqepqlgphDVLIRVVKSGLNPIDYFVIn---aIPVTPMPH-IPGAELAGVVEKVGdhvkgl 83  Sulfolobus solf...
NP_344123      2 MKALTFDKNGIENLKFTDYknpeignhEVLIRVKLAGVNPVDYYTVe---rLKVNPIPH-IPGVEFSGEVVKVGdhvksv 77  Sulfolobus solf...
NP_378253      4 MKALIFEKSGIENLKISDVkeptlgphDVLVKVKMAGVNPIDYFVVn---fIPVTPMPH-IPGAEIYGEVAKVGdhvksv 79  Sulfolobus toko...
YP_001191001  22 MKAILFEKSGLENLRVGEVkdpepgshDVVIRVKESGVNPIDYFVVa---gIQVKPMPH-IPGAEVYGEVEKVGdhvktv 97  Metallosphaera ...
EET90249       1 MKAAVFDKNGIENLKVLDIekpvpasgEALVKVASAAINPIDDRVIn---kVDFGGKPH-IPGAEVAGVVEEVGdsvkgf 76  uncultured eury...
EEZ93240       1 MKAWVLSKNGIDNLNLKEInrpklkhdEVLVKVKAIGLNPIDSMVIdl-ipVKSEIIPGaEFAGEIEEVGEEVKal---- 75  Candidatus Parv...
YP_023624      1 MRAIVLERFGIENIKIEDIdde---spGIPVKITMAGLNPVDYSTVngnimYGVKPMPH-VPGSEAIGIAMADGny---i 73  Picrophilus tor...
Feature 1                                                                               #   #    
YP_001541497  77 kPGDKVVVYGRVFDGTCDLCLASMENLCRNGGIi--GIVTNGGWAEYAIVPDRNLIKLPDdvnWDLAASLPVAALTSYHA 154 Caldivirga maqu...
NP_560184     78 sRGDPVVVYNRLYCGHCRQCLTGWTQMCEVTGGgiiGIVTQGGYAEYAVVPAKNAVATRAd--LKEAATLPIGALTAWNM 155 Pyrobaculum aer...
NP_394771     78 kKGDRVVVYNRVFDGTCDQCISGNEHLCTAGGIw--GVVSNGGYAQKVAVPEKNVFRLPKnvsDEMAASIGVAALTSFRA 155 Thermoplasma ac...
EAY56072      77 rIGDRVTVYSRMFDGNCDMCLSGRENLCRNGTIm--SIGSNGGFVEYVALDEKNAVKIGDeisWEMAASLPIAALTPYHA 154 Leptospirillum ...
YP_001190539  77 sVGDRVAVYTRLFDGTCSSCMRGDQTYCVNGKRv--GVESQGGYAEEIVIPGRNVMKSDLs--EEVLSSLPIAVLTPYHA 152 Metallosphaera ...
NP_343697     84 nKGDKVVVYNRVFDGTCDLCLSGREMLCRNGGIm--SVITNGGWSEYFSVPDKNIFKIPEsmsWDVAASLPVAALTSYHS 161 Sulfolobus solf...
NP_344123     78 sVGDRVTIYGRIFDGTCDMCMAGYETVCRNGGRi--GVDANGGWAEYVAVEEKYVFKLPNeytWEMGSSLTVAALTAYHA 155 Sulfolobus solf...
NP_378253     80 nIGDKVVVYNRVFDGKCDMCLQGMEQLCRNGGIi--SIITNGGFSEYFSVSEHNLVKVEGi-nDEIAASLPVAALTAYHA 156 Sulfolobus toko...
YP_001191001  98 kPGDKVVVYNRVFDGNCDMCLRGDEMLCRNGGIm--SLVTQGGWAEKMVVPEKNLVKVNLd--SALAASLPVAALTSYHA 173 Metallosphaera ...
EET90249      77 sKGDHVIVYPRKFDGTCDMCLAGNEMLCRNGGIf--GLATDGGFREYIAVPEANLIKVPEdmnMELAASIPVAALTAYHA 154 uncultured eury...
EEZ93240      76 kKGDRVSVYNRYFDGTCHYCLSGEEMLCDNGYIf--SIGSNGGLTEYAVINQKNAFKIPDstsFELAASLPVAALTSYNA 153 Candidatus Parv...
YP_023624     74 kRGDRVIIYNRIFDGTCEQCIKGNEHLCLNGGIl--GVASNGVYREMIKLPEMNLFKIPDsidDHVAASMGVGALTAYRA 151 Picrophilus tor...
Feature 1                       #### ##                 ##      #            #                   
YP_001541497 155 LreanlraGETLVVFGASGNTGQFAVQLGKLMGARVIAVSGK-----NWVSELGaDYVASIDnvkdvvEKATdg---rmA 226 Caldivirga maqu...
NP_560184    156 AyrasispGEKVAVVGATGNVGIYAVQFAKLLGGEVYAISRRkakveSILKSAGaDAVLTPDe----aKSAAp------F 225 Pyrobaculum aer...
NP_394771    156 LrlagcapGKSVLIFGASGNTGMFSVQMASMMGCDVYAVSRK-----DWIEEFGaTEVFEADei---pDSMK-------F 220 Thermoplasma ac...
EAY56072     155 LnlsglgpGENFVAFGASGNTGLFALQFAKERGATVMAVSGK-----DWVSEYGaDYLVPRDsv---qPEVAritsnkmA 226 Leptospirillum ...
YP_001190539 153 LrtvgvgvDDTVVVLGASGNTGIFAVQLAKRMGARVIAVTSR-----EWVKEYA-DEVVDYPta---eEEVKrltdggmA 223 Metallosphaera ...
NP_343697    162 LkelevgpNDIIVIFGASGNTGLFAVQLAKKFGATVIAVSRK-----NWLKEFGaDYIVGYDdv---vQKVKeitngkmA 233 Sulfolobus solf...
NP_344123    156 LkeaqlspSQTLVVFGASGNTGMFLVQLGKKFGAKVIAVSRK-----SWLRGYGaDFVVDYNev---eEKVKeitngkmA 227 Sulfolobus solf...
NP_378253    157 Lstv-qvfGKTVVVFGASGNTGQFAVQFAKMMGGYVIAVSNK-----NWVKEFGaDEVVSYDkv---eEKVKeltngrmA 227 Sulfolobus toko...
YP_001191001 174 LketevgvGKTVVVFGASGNTGMFAVQLAKKMGARVIAVSRK-----SWLKEFGaDEIADYSnmkevvEKATng---rmA 245 Metallosphaera ...
EET90249     155 LamarlsaGETLYVVGASGNTGMFAVQLGKIQGAHVVAISGK-----KWLGDFGaDTVVDGEal--kaETSKpdf--kkA 225 uncultured eury...
EEZ93240     154 LnranirkDEFIAVVGASGNTGIFALQFAKMFGAKTIAISSK-----DWVKDFGaDYVVGYEna---lEEVKkitdskmV 225 Candidatus Parv...
YP_023624    152 Lktm-nieAGKTILVYGAGNTGIFTAQLARIFGLETYVVSRK-----KDLERYN-INVLDSVp-----EDFK-------A 212 Picrophilus tor...
Feature 1             ## #                  ##                       ###                         
YP_001541497 227 DVVVDPLGERTWGVSLPLLGrGGRWVTFGQLTGgevkiQLSLLYSNQFKLIGSTGGTRRELLELVNIM--SKLKVKVDKy 304 Caldivirga maqu...
NP_560184    226 DVVLDPTGSASWDLSFGVLGrGGRYVTAGALTGaevrlDLRRLYGMQILVIGATGGRRADFNTVVRLLeaGRIKAFLHNv 305 Pyrobaculum aer...
NP_394771    221 DIVVNPLGTLFWKESLKHLGiRGSLVTFGIFTGregsiDIADLYTGERRILGSTGGTRSDLRDLLEFMkmHDLRVKISRe 300 Thermoplasma ac...
EAY56072     227 DVVMNSLGESVWESSYSALGtDGRLVSFGVLTGksiplDLSGLYSKQLKLIGSTGGTMKEFVELVANA--KRYKVRVWKk 304 Leptospirillum ...
YP_001190539 224 SVVVNSLGEKYWDLGLKLVGnHGKIVTYGGLTGgkvslDVNKLYAKHASIVGTNRGNMAELLELLKLA--KDLKVKVHRy 301 Metallosphaera ...
NP_343697    234 DVVINSLGSSMWENSLQVLGlDGQLAFFGTLTGsevkvNLSSLYGRHIKVVGTTGGSRKELMELINLC--KDCKVKVHKt 311 Sulfolobus solf...
NP_344123    228 DVVINSLGEQFWDKSFSVLGvRGKLVTFGTLLGgnvkvDLSQLYSKHISILGVNRGNRKDFIELLDIC--KDCKVKTWKi 305 Sulfolobus solf...
NP_378253    228 DIVINSVGSSVWDKSLSVLGlNGKLLFFGGITGsnvslDLGAIYGKHASLIGTTGGNRKELVELASMA--KKLKVKVWKv 305 Sulfolobus toko...
YP_001191001 246 DVVINSLGTSAWDASMSVLGrRGKLVVFGTLTGaevklNLSAVYSAHGQIVGTTGGTRAELVELAEIC--SDCKVKVHRe 323 Metallosphaera ...
EET90249     226 NVVVHSIGSKEWDRSMSLLDlNGRLVLFGALTGqdvalNVQDLYARQISIVGSTGGSKKEITELVKMA--KNLKVRVWKr 303 uncultured eury...
EEZ93240     226 DVVIDSIGTKLWDLGYSLLGkNGRMVTFGTETGsnaqiDISQLYSKQLSILGSTGGSIKQFSEVVNKS--GDLKVKTWKk 303 Candidatus Parv...
YP_023624    213 DYIINPLGGSIFEESLRHIKtGGKIVTFGILTGreakiDIGSLYANEIKIYGSTGGTRKDLLELIKIIsmNRIYLPVEKt 292 Picrophilus tor...
Feature 1                               
YP_001541497 305 YELSEAkEALNRLFSPQRNGRIM 327 Caldivirga maquilingensis IC-167
NP_560184    306 YPLADVrKALEELRSPERVGKVL 328 Pyrobaculum aerophilum str. IM2
NP_394771    301 FKLTEM-QDALKFYNEDHDGRIL 322 Thermoplasma acidophilum DSM 1728
EAY56072     305 FGLDEGaEAIRAIRSKERDGRIM 327 Leptospirillum sp. Group II UBA
YP_001190539 302 YTLDEArEAFREFKHGNRDGRIF 324 Metallosphaera sedula DSM 5348
NP_343697    312 YKLDEGvEAVKEIMNENREGRIM 334 Sulfolobus solfataricus P2
NP_344123    306 FKLEEGkEALKELFSKERDGRIF 328 Sulfolobus solfataricus P2
NP_378253    306 RKLEDGkEALQDLFNKNRDGRIL 328 Sulfolobus tokodaii str. 7
YP_001191001 324 YPLEKAaEALRELNSGGRDGRIM 346 Metallosphaera sedula DSM 5348
EET90249     304 FPLEKIvEAFEAEHSEERDGRVM 326 uncultured euryarchaeote ARMAN-2
EEZ93240     304 FNFQEAkEAFKEINNKEKSGRII 326 Candidatus Parvarchaeum acidiphilum ARMAN-4
YP_023624    293 FSLWDL-KEAMNYFKNRSTGRIL 314 Picrophilus torridus DSM 9790

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