1Q5E

Substrate-free Cytochrome P450epoK

1Q5E の概要

• エントリーDOI: 10.2210/pdb1q5e/pdb
• 関連するPDBエントリー: 1PKF 1Q5D
• 分子名称: P450 epoxidase, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• 機能のキーワード: cytochrome p450, epothilone oxydoreductase, heme-enzyme, oxidoreductase
• 由来する生物種: Sorangium cellulosum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47425.81

構造登録者

Nagano, S.,Li, H.,Shimizu, H.,Nishida, C.,Ogura, H.,Ortiz de Montellano, P.R.,Poulos, T.L. (登録日: 2003-08-06, 公開日: 2003-10-28, 最終更新日: 2024-04-03)

主引用文献

Nagano, S.,Li, H.,Shimizu, H.,Nishida, C.,Ogura, H.,Ortiz de Montellano, P.R.,Poulos, T.L.
Crystal structures of epothilone D-bound, epothilone B-bound, and substrate-free forms of cytochrome P450epoK
J.Biol.Chem., 278:44886-44893, 2003

PubMed Abstract: Epothilones are potential anticancer drugs that stabilize microtubules by binding to tubulin in a manner similar to paclitaxel. Cytochrome P450epoK (P450epoK), a heme containing monooxygenase involved in epothilone biosynthesis in the myxobacterium Sorangium cellulosum, catalyzes the epoxidation of epothilones C and D into epothilones A and B, respectively. The 2.10-, 1.93-, and 2.65-A crystal structures reported here for the epothilone D-bound, epothilone B-bound, and substrate-free forms, respectively, are the first crystal structures of an epothilone-binding protein. Although the substrate for P450epoK is the largest of a P450 whose x-ray structure is known, the structural changes along with substrate binding or product release are very minor and the overall fold is similar to other P450s. The epothilones are positioned with the macrolide ring roughly perpendicular to the heme plane and I helix, and the thiazole moiety provides key interactions that very likely are critical in determining substrate specificity. Interestingly, there are strong parallels between the epothilone/P450epoK and paclitaxel/tubulin interactions. Based on structural similarities, a plausible epothilone tubulin-binding mode is proposed.

PubMed: 12933799
DOI: 10.1074/jbc.M308115200

実験手法

X-RAY DIFFRACTION (2.65 Å)