Conserved Protein Domain Family
6_hydroxyhexanoate_dh_like

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cd08240: 6_hydroxyhexanoate_dh_like 
6-hydroxyhexanoate dehydrogenase
6-hydroxyhexanoate dehydrogenase, an enzyme of the zinc-dependent alcohol dehydrogenase-like family of medium chain dehydrogenases/reductases catalyzes the conversion of 6-hydroxyhexanoate and NAD(+) to 6-oxohexanoate + NADH and H+. 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: 176202
View PSSM: cd08240
Aligned: 21 rows
Threshold Bit Score: 385.045
Threshold Setting Gi: 260805428
Created: 2-Jul-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
putative NAD(P)catalytic Zn
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                                             ###  #                                     
BAC80217       1 MHCYCVTHHGQPLEDVEKEIPQPKGtEVLLHVKAAGLCHTDLHLWEGYYDLgggkrlsladrGLKPPLTLSHEITGQVVA 80  Acinetobacter s...
YP_001414606   1 MKSEAIVEYGQPLQILEGETPQPKGtEVLLKVTHCGVCHSDVHIHDGYFDMgggnq-ldvraGRKLPFTLGHEIEGEVVA 79  Parvibaculum la...
XP_002115526   1 MKAAQVVEAGAPLQLQEVPLPKATHdEVVIKVISVGVCHSDLHLWDGGYDL-----------GGHYPVTPGHEIVGSVHQ 69  Trichoplax adha...
YP_552310      6 AHRWAFPTWGAALSEHTDELAAPSGhEVSIRVTHCGMCHSDLHIQAGGFDMgggkltsleraGATLPLTMGHEIGGEVVE 85  Polaromonas sp....
YP_587673      1 MKSYDIVEWGKPLQEVLRDRPKPVGtEVLVKVQACGICHSDLHIRDGLLDLgngkhisfesvGVKLPFTMGHEIVGVVAE 80  Ralstonia metal...
AAQ62392       1 MKSYQVFENAQPIKEVELDTPIPEGdEVLIKTIACGVCHTDIHIHDGFFDIgngk---kmtsRMVQPLAMGHEVFGEVVS 77  uncultured mari...
NP_948406      4 MRRQSLVKFDAPLCETIIDAPKPQGrEVLVKIERCGLCHSDLHIQDGYADLgggkk-ldttrGMTLPFTLGHEIAGVVAE 82  Rhodopseudomona...
ABZ08425       1 MKAAQIIEPNKPLKISEIDTPTPTGkQVLVKVKAVGVCHSDLHLWEGGYDTgdgfm-kvtdrGVKFPVIPGHEVVGTVAE 79  uncultured mari...
XP_002122007   1 MKKAEIVEAKKPLKISEAPVPKPPKdGAVVKLLYSGICHSDIHQIDNGFDVgsrftcltddpNYQFPIVPGHEMAGVVHS 80  Ciona intestinalis
XP_002128057   2 MKKAEIVGLNKPLRIVQVDIPATPKkGAIVKVAYSGVCHSDIHQWDDCIDLgntkiglsdaiGYKLPVVPGHEISGTVYS 81  Ciona intestinalis
Feature 1                                                                                        
BAC80217      81 VGPDa---ESVKVGMVSLVHPWIGCGECNYCKRGeENLCAKPQQLGIa-----kPGGFAEYIIVPHPRYLvDIAGLDLae 152 Acinetobacter s...
YP_001414606  80 TGPDa---KEVEIGAHRVAYPWIGCGECPTCNRGdEHLCNKPRNLGIq-----vAGGYATHVLVPHPRYLlDYEGVADgl 151 Parvibaculum la...
XP_002115526  70 MGDEv---VDFAVGDNVLVFPWIGCGQCPICQAGdDNVCDKPRSIGIf-----cNGGYAEYVIIPSYKYLaKISGVDFha 141 Trichoplax adha...
YP_552310     86 IGPEv---TGLALGDKVIVYPWLGCGQCAVCLRGdDHLCPRAARNLGiq----lPGGYADMVRVPHSRYLvPIGTLEPar 158 Polaromonas sp....
YP_587673     81 AGSE----ASVKAGTPCVVYPWHGCGTCLNCTNGrEVDCESGRALGTr-----kPGGYSDYVVVPHEQYLlDYGNLDPll 151 Ralstonia metal...
AAQ62392      78 FGQNv---KNIEVGKKFVVYPWIGCGECEPCQADnEHECGPLTAENIgv---avDGGYGEYVLVKHSKYLfDAGNTPDdl 151 uncultured mari...
NP_948406     83 VGPDa---PQDLIGTKKAVFPWIGCGKCRDCLAGdENLCAKNRFLGVs-----iDGGFATHVLVPDAKYLlDYDPLPTnv 154 Rhodopseudomona...
ABZ08425      80 IGDSv---EGIRVGDDVLVYPWIGCGSCPTCEKGdTNLCEAPQSLGVf-----qDGGYAEYSLIPDYKFLaKISGIDLeg 151 uncultured mari...
XP_002122007  81 LGENak-pCDLKIGDRVAVFPWIGCGKCGYCDNGySQFCKEKHHTMGfga--vpGGYSNYTVVIHHQFLVkVPASIPLsi 157 Ciona intestinalis
XP_002128057  82 IGEEadaaAGLKVGDRVAVYPWIGCSKCGVCTHG-KSECCKERQLTIigvgassGGHSTHVAVTEVQFVVkLPDSIPLdl 160 Ciona intestinalis
Feature 1             #   #                           ######                    ##   #           
BAC80217     153 AAPLACAGVTTYSALKKFgdli-------qsePVVIIGAGGLGLMALELLKAMQa--KGAIVVDIDDSKLEAARAAGAL- 222 Acinetobacter s...
YP_001414606 152 AATYMCSGLTAYGAMKKLgdis-------peeRVMVVGLGGVGMMGLQFAKAMFp--AAPLGADVDDNKLQSAKGAGAH- 221 Parvibaculum la...
XP_002115526 142 ATSLACSGLTAYNAIKKAnvr--------speYLVIIGTGGLGLMGIQLAKATTq--AKIICVDIDDQKLNIAKNLGAD- 210 Trichoplax adha...
YP_552310    159 AATFACAGITAYGAIRKLnpmt-------aedHVAIIGCGGVGMTAVALLSATSk--ARIVAIDPDPAKREAALRYGAV- 228 Polaromonas sp....
YP_587673    152 AATCACSGLTSFSALKKLppml-------eadTLVLIGAGGLGLAALGLAPQLTs--ARLVVADIDDEKLARASAAGAH- 221 Ralstonia metal...
AAQ62392     152 AGSYACRGLTAYSSLKKAnlkp-------nenKLVIISAGGLGLLALKIAKAAFn--VSPIVVDIDDSKLEIAKAAGAS- 221 uncultured mari...
NP_948406    155 AATLMCSGITAYGALKRLvdrp-------rqrNLLLIGLGGVGMMGLSLAQAMFk--QPIAVADLSPAAREAALKNGAA- 224 Rhodopseudomona...
ABZ08425     152 AASLACSGLTAYTAVKKAisn--------speNILIIGAGGLGLMGVQITKALCn--ANIICADLDDERLKKAIELGAD- 220 uncultured mari...
XP_002122007 158 ATMLPCSGLTTYNAVTTAlpaikkatafkgkaSMLIIGAGGLGLWALQLAKNILpktTNVVVADLSESKLGNAKERGADg 237 Ciona intestinalis
XP_002128057 161 ACMLPCSGLTTYNAVTSVldtvekatlyhgkaSVLIIGAGGLGLWSLRLAQALFpptTEITVADISEEKLKVAKDRGCHd 240 Ciona intestinalis
Feature 1             #                                ## #                     ##               
BAC80217     223 -SVINSRSeda-----aqqLIQATDG-----GARLILDLVGSNpTLSLALASAA--RGGHIVICGLMGGEIKLSIPVIPM 289 Acinetobacter s...
YP_001414606 222 -EVYNPKDpea-----ikkVLADSNG-----GVPAAVDFVGSEaSLKFATSIVR--KGGQVIVVGLFGGGFSMPIPLFPM 288 Parvibaculum la...
XP_002115526 211 -FIVNSSDgna-----vqkIYSICPK-----GVDSVVDFVNASpTAKIGLSILK--KRGNLVLVGLFGGSIEISLVTIPL 277 Trichoplax adha...
YP_552310    229 -LAFDPNEaga-----lrtIGKACNN-----DIAGVVDFVGAEsTSSLAVNLVR--RTGQVVIVGLFGGEFRMPLPMFAI 295 Polaromonas sp....
YP_587673    222 -EVVNLRSena-----ardLRKAAPN-----GIRAIVDFVGSAqTTGVALESVA--RGGTVVVVGLFGGAISLSTALLPM 288 Ralstonia metal...
AAQ62392     222 -EVINSSHega-----kkrIMDLTEG-----GATTVIDYVGAEaSIQFGYDLFGfnKNGLYILVGMLGGKFEVQLPLMTF 290 uncultured mari...
NP_948406    225 -VAYDPSEpdv-----akrIFKETDG-----GFDGVVDFAGNDkSMNFAVSTVA--RGGKIVVSGLMGGQFSLPMVQWIY 291 Rhodopseudomona...
ABZ08425     221 -NVINTNAigygqpeasknIMSICNGk----GVDSIIDFVNAPpTFKLGLSVLR--KRGNVVLVGLFGGAANLSLVTIPL 293 uncultured mari...
XP_002122007 238 tVAWDPSKse-------edLIKATAKlgneiGYDAIIDFVNTRvTSTRAFECLN--TDGLQVCVGLFGGSGNFPLPVLTL 308 Ciona intestinalis
XP_002128057 241 -TVFWDRSlsaad--lhkaTISKGNKg----GFDAIMDFVNSQvTAERAFRCLK--PYGLHVMVGLFGGAATFPLPMLTL 311 Ciona intestinalis
Feature 1               ###                                                    
BAC80217     290 RPLTIQGSYVGTVEELRELVELV-KETHMSAIPVkKLPISqINSAFGDLKdGNVIGRIVLMH 350 Acinetobacter sp. NCIMB9871
YP_001414606 289 RALSIGGSYVGSLTETKEMMELV-KAGKIDPIPVsERRLGeGSKSLDDLRkGSVMGRVVLKP 349 Parvibaculum lavamentivorans DS-1
XP_002115526 278 KTLIIQGAYTGTYREMVELLQLA-KEGIINPIISkQYSLQeANTALNDLKqRKIVGRAVIIP 338 Trichoplax adhaerens
YP_552310    296 KSLQITGSYVAGLEDLRELVALA-QRVDLPQIPLeLRPMAsVNQALDDLAhGRVIGRVVLQP 356 Polaromonas sp. JS666
YP_587673    289 RNVTLRGSYVGSVEEMRALLDLLqEKGKGSPVNLkSLPMSaVNEALEELAqGRVAGRLLAIP 350 Ralstonia metallidurans CH34
AAQ62392     291 SSRVLQGSYLGSIQEMKELMDLV-RAGKIEPVPVeARHVSmANDTIADLKaGNIPGLVCLKH 351 uncultured marine gamma proteobac...
NP_948406    292 KRMTVEGFMVGTLEETKELLALA-RAGKVKPTPMkEEPMQdAQKWIDQLRaGKVVGRIMLAN 352 Rhodopseudomonas palustris CGA009
ABZ08425     294 KAITIQGAYTGNYNDMIELLDLA-KRGVIKPIISkHYSLDeVNNALEDLKnRKIVGRSVINP 354 uncultured marine crenarchaeote H...
XP_002122007 309 SEKGVKGVYVGRLQQLKDLIALV-STNKLTPPPLiYYKLEdINSALDLLRvGKINGRGIIKH 369 Ciona intestinalis
XP_002128057 312 GARQIKGVYVGSLQQFNELIDLV-SKNKLDPPPLnYFKLNdVTKAFTLLKeGKINGRGLIKH 372 Ciona intestinalis

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