2XFH

Structure of cytochrome P450 EryK cocrystallized with inhibitor clotrimazole.

「2VRV」から置き換えられました

2XFH の概要

• エントリーDOI: 10.2210/pdb2xfh/pdb
• 関連するPDBエントリー: 2JJN 2JJO 2JJP 2VRV 2WIO
• 分子名称: ERYTHROMYCIN B/D C-12 HYDROXYLASE, PROTOPORPHYRIN IX CONTAINING FE, 1-[(2-CHLOROPHENYL)(DIPHENYL)METHYL]-1H-IMIDAZOLE, ... (5 entities in total)
• 機能のキーワード: monoxygenase, erythromycin a biosynthesis, oxidoreductase
• 由来する生物種: SACCHAROPOLYSPORA ERYTHRAEA
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46731.33

構造登録者

Savino, C.,Montemiglio, L.C.,Gianni, S.,Vallone, B. (登録日: 2010-05-24, 公開日: 2010-09-29, 最終更新日: 2023-12-20)

主引用文献

Montemiglio, L.C.,Gianni, S.,Vallone, B.,Savino, C.
Azole Drugs Trap Cytochrome P450 Eryk in Alternative Conformational States.
Biochemistry, 49:9199-, 2010

PubMed Abstract: EryK is a bacterial cytochrome P450 that catalyzes the last hydroxylation occurring during the biosynthetic pathway of erythromycin A in Streptomyces erythraeus. We report the crystal structures of EryK in complex with two widely used azole inhibitors: ketoconazole and clotrimazole. Both of these ligands use their imidazole moiety to coordinate the heme iron of P450s. Nevertheless, because of the different chemical and structural properties of their N1-substituent group, ketoconazole and clotrimazole trap EryK, respectively, in a closed and in an open conformation that resemble the two structures previously described for the ligand-free EryK. Indeed, ligands induce a distortion of the internal helix I that affects the accessibility of the binding pocket by regulating the kink of the external helix G via a network of interactions that involves helix F. The data presented thus constitute an example of how a cytochrome P450 may be selectively trapped in different conformational states by inhibitors.

PubMed: 20845962
DOI: 10.1021/BI101062V

実験手法

X-RAY DIFFRACTION (1.9 Å)