6CXX
Horse liver E267H alcohol dehydrogenase complex with 3'-dephosphocoenzyme A
Summary for 6CXX
| Entry DOI | 10.2210/pdb6cxx/pdb |
| Related | 1JU9 1QKH 1YE3 5VKR 6CY3 |
| Descriptor | Alcohol dehydrogenase E chain, ZINC ION, DEPHOSPHO COENZYME A, ... (6 entities in total) |
| Functional Keywords | nad-dependent horse liver alcohol dehydrogenase e267h mutant 3'-dephosphocoenzyme a, oxidoreductase |
| Biological source | Equus caballus (Horse) |
| Total number of polymer chains | 2 |
| Total formula weight | 82070.40 |
| Authors | Plapp, B.V. (deposition date: 2018-04-04, release date: 2018-04-25, Last modification date: 2023-10-04) |
| Primary citation | Kim, Y.H.,Gogerty, D.S.,Plapp, B.V. Substitutions of a buried glutamate residue hinder the conformational change in horse liver alcohol dehydrogenase and yield a surprising complex with endogenous 3'-Dephosphocoenzyme A. Arch. Biochem. Biophys., 653:97-106, 2018 Cited by PubMed Abstract: Glu-267 is highly conserved in alcohol dehydrogenases and buried as a negatively-charged residue in a loop of the NAD coenzyme binding domain. Glu-267 might have a structural role and contribute to a rate-promoting vibration that facilitates catalysis. Substitutions of Glu-267 with histidine or asparagine residues increase the dissociation constants for the coenzymes (NAD by ∼40-fold, NADH by ∼200-fold) and significantly decrease catalytic efficiencies by 16-1200-fold various substrates and substituted enzymes. The turnover numbers modestly change with the substitutions, but hydride transfer is at least partially rate-limiting for turnover for alcohol oxidation. X-ray structures of the E267H and E267 N enzymes are similar to the apoenzyme (open) conformation of the wild-type enzyme, and the substitutions are accommodated by local changes in the structure. Surprisingly, the E267H and E267 N enzymes have endogenous (from the expression in E. coli) 3'-dephosphocoenzyme A bound in the active site with the ADP moiety in the NAD binding site and the pantethiene sulfhydryl bound to the catalytic zinc. The kinetics and crystallography show that the substitutions of Glu-267 hinder the conformational change, which occurs when wild-type enzyme binds coenzymes, and affect productive binding of substrates. PubMed: 30018019DOI: 10.1016/j.abb.2018.07.003 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.26 Å) |
Structure validation
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