4JLT
Crystal structure of P450 2B4(H226Y) in complex with paroxetine
Summary for 4JLT
| Entry DOI | 10.2210/pdb4jlt/pdb |
| Related | 1PO5 1SUO 2BDM 2Q6N 3G5N 3G93 3KW4 3ME6 3MVR 3R1A 3R1B 3TK3 3TMZ 3UAS 4H1N |
| Descriptor | Cytochrome P450 2B4, PROTOPORPHYRIN IX CONTAINING FE, 5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE, ... (8 entities in total) |
| Functional Keywords | p450, cytochrome p450 2b4, monooxygenase, oxidoreductase, me protein, cyp 2b4 |
| Biological source | Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits) |
| Cellular location | Endoplasmic reticulum membrane; Peripheral membrane protein: P00178 |
| Total number of polymer chains | 1 |
| Total formula weight | 57264.94 |
| Authors | Shah, M.B.,Pascual, J.,Stout, C.D.,Halpert, J.R. (deposition date: 2013-03-13, release date: 2013-06-26, Last modification date: 2023-09-20) |
| Primary citation | Shah, M.B.,Kufareva, I.,Pascual, J.,Zhang, Q.,Stout, C.D.,Halpert, J.R. A Structural Snapshot of CYP2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States. J.Pharmacol.Exp.Ther., 346:113-120, 2013 Cited by PubMed Abstract: An X-ray crystal structure of CYP2B4 in complex with the drug paroxetine [(3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine] was solved at 2.14 Å resolution. The structure revealed a conformation intermediate to that of the recently solved complex with amlodipine and that of the more compact complex with 4-(4-chlorophenyl)imidazole in terms of the placement of the F-G cassette. Moreover, comparison of the new structure with 15 previously solved structures of CYP2B4 revealed some new insights into the determinants of active-site size and shape. The 2B4-paroxetine structure is nearly superimposable on a previously solved closed structure in a ligand-free state. Despite the overall conformational similarity among multiple closed structures, the active-site cavity volume of the paroxetine complex is enlarged. Further analysis of the accessible space and binding pocket near the heme reveals a new subchamber that resulted from the movement of secondary structural elements and rearrangements of active-site side chains. Overall, the results from the comparison of all 16 structures of CYP2B4 demonstrate a cluster of protein conformations that were observed in the presence or absence of various ligands. PubMed: 23633618DOI: 10.1124/jpet.113.204776 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.14 Å) |
Structure validation
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