Conserved Protein Domain Family
MDR_like_2

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cd05289: MDR_like_2 
alcohol dehydrogenase and quinone reductase-like medium chain degydrogenases/reductases
Members identified as zinc-dependent alcohol dehydrogenases and quinone oxidoreductase. QOR catalyzes the conversion of a quinone + NAD(P)H to a hydroquinone + NAD(P)+. Quinones are cyclic diones derived from aromatic compounds. Membrane bound QOR actin the respiratory chains of bacteria and mitochondria, while soluble QOR acts to protect from toxic quinones (e.g. DT-diaphorase) or as a soluble eye-lens protein in some vertebrates (e.g. zeta-crystalin). QOR reduces quinones through a semi-quinone intermediate via a NAD(P)H-dependent single electron transfer. QOR is a member of the medium chain dehydrogenase/reductase family, but lacks the zinc-binding sites of the prototypical alcohol dehydrogenases of this group. 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: 176191
View PSSM: cd05289
Aligned: 215 rows
Threshold Bit Score: 177.367
Threshold Setting Gi: 211592157
Created: 4-Aug-2005
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
putative NAD(P)
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                                                 ###  #                                 
ACM40032       1 MKAIIINEYGdnsv-lkyaDVKDPepk-agEVLVKVhAAGVNPVDWKirsgagq-rmgmtlPIHLGGEIAGiVEKLGpgv 77  Agrobacterium v...
CAJ88075       1 MKAFMIERYGdrdg-grvtEAPDPqvg-adDVLVRVrAASVNPLDLRirdggfkailpyrlPLVLGNDLAGvVVEVGsdv 78  Streptomyces am...
NP_745132      7 MQALTFKRYGkspd-iglaDVPRPtpk-adELLVQVhAAGLNPIDNMiptgmfkpvlhfqlPATLGSDLAGiVTEVGsnv 84  Pseudomonas put...
YP_001279899   1 MKAAYINHYGkldq-iqfgDQPKPtiq-sdEVLVKVhAVSINPLDLRmvegefkavipvqfPFILGNDLAGvIVEVGtev 78  Psychrobacter s...
YP_001792666   1 MKALTFQRYGkspd-igfaDIPRPtlk-pdELLVQVhAVGLNPIDNIipkgtfkpvlhfklPATLGSDLAGvVIEVGsrv 78  Leptothrix chol...
YP_001535936   1 MQAYVQTKYGdpsv-mrlmDVPKPtpe-hgEVLIRVrAAGLNPVDYHlrqgkmrmiarlklPRVAGSELAGvVEAVGpgv 78  Salinispora are...
YP_861961      1 MKALQITKYGdfkdslqfnEVDKPeis-enEILIAVkAVSLNPIDYKivegnlkemlkldfPATVGYDVSGeVVEIGsav 79  Gramella forset...
XP_505149      1 MKAAYTTGYGgpdkiqyseDHPKTtliaddHVLIRVaAASLNPIDGMrnrgflkmlapdkhPHIFGYDVSGvVEEVGlgv 80  Yarrowia lipoly...
XP_502315      1 MRAAFTTAYGgpdkieysdSLPKVklggddHVLIRVaDASINPIDGLrnrgmlrilmcddhPHVFGYDVGGfVEEVGskc 80  Yarrowia lipoly...
EEY61339       1 MRTWFYSKYGgptv-mqtgDQPDPdlggpkDVVVKVhAASLNPIDYKrrqgvlkmllentwPHIVGYDFSGvVTNCGddv 79  Phytophthora in...
Feature 1                                                        #   #                     ######
ACM40032      78 teFNRGDGVYGvi---kqGGFAQYAIAnttdVARKPstLDFIETAATPLGALTAWQAMfdvaklstGQHVFITNSSGGVG 154 Agrobacterium v...
CAJ88075      79 trFAVGDEVYArpdkdriGTFAELIAVhendLASKPagLTMVEAASLPLVALTSWQALveraqvqpGQKVLIHGGSGGVG 158 Streptomyces am...
NP_745132     85 trFKPGDAVFAslfdlgtGAIAEFAVVpesaAALKPanLSFEQAASIPMVGLTSWQALkerlklqaGQKVFIPAGSGGIG 164 Pseudomonas put...
YP_001279899  79 erFKVGDKVFAktd--eqGSFAEYTSLkeasVALKPknISMTQAASLPLVTLTAWQALveiaqlkrGQKVLIHAGSGGVG 156 Psychrobacter s...
YP_001792666  79 trFKPGDAVFAsvfdlgtGTLAEFAVVpervAALKPpnLDFVQAASVPMVGLTSWQALkeraglgsGKKVFIPAGSGGIG 158 Leptothrix chol...
YP_001535936  79 tnLAVGDRVFTrvdvmklGAFAPYAVVaadlVAPMPqsLDFTEAAGLPLAGLTALQALrdelniekGQRIFISGGAGGVG 158 Salinispora are...
YP_861961     80 knFKIGDAVFGrvpqeymGTLAEFVAVdsavMAHKPeeISFEKASSLPLVGLTAIQALekag-lkkDDRVLIHAGSGGVG 158 Gramella forset...
XP_505149     81 deFKAGDRVYSrigerqdGTMAEFVSVksslVARAPsnISLQDAAGIPLVGLTSMQAFeagn-lqrDQTIFISKGSGGIG 159 Yarrowia lipoly...
XP_502315     81 tnLKVGDRVYGrigesqsGTLAGYVSAqesvIAVAPtnLPLSETAGVPLVGLTAYQALragd-vqpGQRVFISKGAGGVG 159 Yarrowia lipoly...
EEY61339      80 dkFALGDEVFGmlphfsnGALADFVVVkadyISKKPsnLTHVEAAALPLVTQTALQCFrlgq-laeNKKVLITGGAGGAG 158 Phytophthora in...
Feature 1                            ## #             #                   ##                    #
ACM40032     155 SLAVQLAka--rGAHVTAMASArNEEYVRSLGaDEFVDYtrqpfe-nsvrdMDVVFDTVGgetFKRAFTTLRqdGFLVTA 231 Agrobacterium v...
CAJ88075     159 TVALQLArr--lGAHVATTASAaKADLVRELGaDLVVDYrtqdfe-evldgYDVVLDTLGgatLQKSLRILKpgGKVVSI 235 Streptomyces am...
NP_745132    165 TFAIQLAkh--lGAKVGTTTSTgNVDLVRALGaDEVVDYktqdfe-tvlrdYDAVLGTVRgdaIEKSLSILRpgSQIVSL 241 Pseudomonas put...
YP_001279899 157 SVAIQLAkh--lGAYVATTASAkNADWIKDLGaDLVIDYktsnft-divsdYDVVFDTQGgdiLEQSLQVLKrgGIVVSI 233 Psychrobacter s...
YP_001792666 159 TFAIQLAkh--lGAKVATTVSTgNVELVRGLGaDEIVDYrtqafe-qvlqgCDAVLGTVRgdaIEKSIGILKpgGRIVSL 235 Leptothrix chol...
YP_001535936 159 TLAIQLAaw--mGAHVATTASPaGENLVRSLGaETVLNYqttsfk-dvlrdYDAVLDLRGgqdLADSFAIVRpgAKVVSV 235 Salinispora are...
YP_861961    159 SFAIQYAka--kGAIVYTTTSKtNMDWVKALGaDRVIDYknedyk-evsnnLDIVFDTLGddyTFEAFDIIEkgGSVTSI 235 Gramella forset...
XP_505149    160 TFAIQLAkn-vyGAKVITTASSkKMDLLRQLGaDQVINYrttvfk-nvvsdVDYALDVSNq--PHAHVSITKknGFVGSL 235 Yarrowia lipoly...
XP_502315    160 TIAIQLAkh-vfGAYVITTGSDhKAELLKELGaDEVINYrkekfqdvikepVDFAFDVSDe--PAAHAKITKknGFVAAL 236 Yarrowia lipoly...
EEY61339     159 SMAIQIAksvfkARTVATTASTkKLERMRLLGaDEVVDYgherfe-relaeYDFALDCTAe--AKQCFECITrgGSVVSI 235 Phytophthora in...
Feature 1        #                                               ###                             
ACM40032     232 Vafps------------------------------------dedKQHGVGVarvqcvpnsqeLTQIRELIeaGKVKPYVa 275 Agrobacterium v...
CAJ88075     236 Agppdadfarelganpvlrq------amnalswrtrrrakrqgvTYSFLFMkad-----ggrLGELTRLVdaGDIRPVVd 304 Streptomyces am...
NP_745132    242 Vgpldaafarakrlnllltf------vfglmsrkimrlakrrnvQYSFLFVqpd-----gaqLAEIGKLLdaQQIQPVId 310 Pseudomonas put...
YP_001279899 234 Agqpdknmaeainanwlmsk------iipllslpirikakkrgvRYHFLFMqpn-----geqLSHIAELVdaENIIPVLd 302 Psychrobacter s...
YP_001792666 236 Vgpldaafararglnfiltf------vfglmsrkvrrlagkrevDYSFLFVrpd-----geqLKGIGDLLesGRIRPVId 304 Leptothrix chol...
YP_001535936 236 Agvpernsatdlgagplvga------lfnllsgkvrrqakahgvTYRYLFMhps-----gadLRILADLVdgGNLKVVTd 304 Salinispora are...
YP_861961    236 Vgppdpetakqmgmedy------------qmpeilselikeksaNYTLTWMqpn-----aeqLKEIKTMVedRTIRPVId 298 Gramella forset...
XP_505149    236 Ngtpspetvedtlsvkpgalv---ssllrsvafvttrcawiygvRYQAIVCrps-----gkqLAIITEYIeaGKIKPVTd 307 Yarrowia lipoly...
XP_502315    237 Rgapspatakkilahppgflmn--nvlraanfatsrtawwygvrYEAIYCVpsa------kdLDTLRGYLekGTIKPIVd 308 Yarrowia lipoly...
EEY61339     236 AetptwkslstgdlqgvsvsyllgvlldclsssvtrrarqaqitYEYMFVVadg------avMDEIRQLAeqRSITPVId 309 Phytophthora in...
Feature 1                                   
ACM40032     276 tVLPFesvkeALEFSEDGht-rGKIVL 301 Agrobacterium vitis S4
CAJ88075     305 rVFPFertreAMEYAEKGsaraGKVVV 331 Streptomyces ambofaciens ATCC 23877
NP_745132    311 rVFPFedakgALEYLAQGrs-kGKVVI 336 Pseudomonas putida KT2440
YP_001279899 303 qVYDFadfakAIQHVDNGhs-kGKVVV 328 Psychrobacter sp. PRwf-1
YP_001792666 305 qVFPFeqakeALDYLALGha-rGKVVV 330 Leptothrix cholodnii SP-6
YP_001535936 305 qVFPFeeiadAFAHLERGra-kGKIIV 330 Salinispora arenicola CNS-205
YP_861961    299 lIYSFqdavkAFEYLADGha-qGKVIV 324 Gramella forsetii KT0803
XP_505149    308 cVFDLkdakeAVKKLEAGha-tGKIIV 333 Yarrowia lipolytica CLIB122
XP_502315    309 cTYDLkdaklAMEKLESGra-tGKIIL 334 Yarrowia lipolytica CLIB122
EEY61339     310 kVFPFekadmAMEYLEAGha-mGKVVV 335 Phytophthora infestans T30-4

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