1TQN
Crystal Structure of Human Microsomal P450 3A4
Summary for 1TQN
| Entry DOI | 10.2210/pdb1tqn/pdb |
| Related | 1PQ2 |
| Descriptor | cytochrome P450 3A4, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total) |
| Functional Keywords | p450, cyp3a4, monooxygenase, drug metabolizing enzyme, oxidoreductase, heme |
| Biological source | Homo sapiens (human) |
| Cellular location | Endoplasmic reticulum membrane; Single-pass membrane protein: P08684 |
| Total number of polymer chains | 1 |
| Total formula weight | 56211.12 |
| Authors | Yano, J.K.,Wester, M.R.,Schoch, G.A.,Griffin, K.J.,Stout, C.D.,Johnson, E.F. (deposition date: 2004-06-17, release date: 2004-07-27, Last modification date: 2024-02-14) |
| Primary citation | Yano, J.K.,Wester, M.R.,Schoch, G.A.,Griffin, K.J.,Stout, C.D.,Johnson, E.F. The Structure of Human Microsomal Cytochrome P450 3A4 Determined by X-ray Crystallography to 2.05-A Resolution J.Biol.Chem., 279:38091-38094, 2004 Cited by PubMed Abstract: The structure of P450 3A4 was determined by x-ray crystallography to 2.05-A resolution. P450 3A4 catalyzes the metabolic clearance of a large number of clinically used drugs, and a number of adverse drug-drug interactions reflect the inhibition or induction of the enzyme. P450 3A4 exhibits a relatively large substrate-binding cavity that is consistent with its capacity to oxidize bulky substrates such as cyclosporin, statins, taxanes, and macrolide antibiotics. Family 3A P450s also exhibit unusual kinetic characteristics that suggest simultaneous occupancy by smaller substrates. Although the active site volume is similar to that of P450 2C8 (PDB code: 1PQ2), the shape of the active site cavity differs considerably due to differences in the folding and packing of portions of the protein that form the cavity. Compared with P450 2C8, the active site cavity of 3A4 is much larger near the heme iron. The lower constraints on the motions of small substrates near the site of oxygen activation may diminish the efficiency of substrate oxidation, which may, in turn, be improved by space restrictions imposed by the presence of a second substrate molecule. The structure of P450 3A4 should facilitate a better understanding of the substrate selectivity of the enzyme. PubMed: 15258162DOI: 10.1074/jbc.C400293200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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