4JLT

Crystal structure of P450 2B4(H226Y) in complex with paroxetine

4JLT の概要

• エントリーDOI: 10.2210/pdb4jlt/pdb
• 関連するPDBエントリー: 1PO5 1SUO 2BDM 2Q6N 3G5N 3G93 3KW4 3ME6 3MVR 3R1A 3R1B 3TK3 3TMZ 3UAS 4H1N
• 分子名称: Cytochrome P450 2B4, PROTOPORPHYRIN IX CONTAINING FE, 5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE, ... (8 entities in total)
• 機能のキーワード: p450, cytochrome p450 2b4, monooxygenase, oxidoreductase, me protein, cyp 2b4
• 由来する生物種: Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits)
• 細胞内の位置: Endoplasmic reticulum membrane; Peripheral membrane protein: P00178
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57264.94

構造登録者

Shah, M.B.,Pascual, J.,Stout, C.D.,Halpert, J.R. (登録日: 2013-03-13, 公開日: 2013-06-26, 最終更新日: 2023-09-20)

主引用文献

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

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: 23633618
DOI: 10.1124/jpet.113.204776

実験手法

X-RAY DIFFRACTION (2.14 Å)