6OO9
Human CYP3A4 bound to a drug mibefradil
Summary for 6OO9
| Entry DOI | 10.2210/pdb6oo9/pdb |
| Descriptor | Cytochrome P450 3A4, PROTOPORPHYRIN IX CONTAINING FE, (1S,2S)-2-(2-{[3-(1H-benzimidazol-2-yl)propyl](methyl)amino}ethyl)-6-fluoro-1-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, ... (6 entities in total) |
| Functional Keywords | substrate, complex, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 57072.20 |
| Authors | Sevrioukova, I.F. (deposition date: 2019-04-22, release date: 2019-09-11, Last modification date: 2023-10-11) |
| Primary citation | Sevrioukova, I.F. Structural Insights into the Interaction of Cytochrome P450 3A4 with Suicide Substrates: Mibefradil, Azamulin and 6',7'-Dihydroxybergamottin. Int J Mol Sci, 20:-, 2019 Cited by PubMed Abstract: Human cytochrome P450 3A4 (CYP3A4) is the most important drug-metabolizing enzyme. Some drugs and natural compounds can act as suicide (mechanism-based) inactivators of CYP3A4, leading to unanticipated drug-drug interactions, toxicity and therapeutic failures. Despite significant clinical and toxicological implications, the mechanism-based inactivation remains incompletely understood. This study provides the first direct insights into the interaction of CYP3A4 with three suicide substrates: mibefradil, an antihypertensive drug quickly withdrawn from the market; a semi-synthetic antibiotic azamulin; and a natural furanocoumarin, 6',7'-dihydroxybergamottin. Novel structural findings help better understand the suicide substrate binding and inhibitory mechanism, and can be used to improve the predictability of the binding ability, metabolic sites and inhibitory/inactivation potential of newly developed drugs and other chemicals relevant to public health. PubMed: 31480231DOI: 10.3390/ijms20174245 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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