2JJP

Structure of cytochrome P450 EryK in complex with inhibitor ketoconazole (KC)

2JJP の概要

• エントリーDOI: 10.2210/pdb2jjp/pdb
• 関連するPDBエントリー: 2JJN 2JJO 2VRU 2VRV 2WIO
• 分子名称: CYTOCHROME P450 113A1, PROTOPORPHYRIN IX CONTAINING FE, 1-ACETYL-4-(4-{[(2S,4R)-2-(2,4-DICHLOROPHENYL)-2-(1H-IMIDAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL]METHOXY}PHENYL)PIPERAZINE, ... (5 entities in total)
• 機能のキーワード: iron, heme, monooxygenase, metal-binding, antibiotic biosynthesis, tie-rod mechanism of action, oxidoreductase, substrate specificity
• 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: 46687.07

構造登録者

Savino, C.,Sciara, G.,Miele, A.E.,Kendrew, S.G.,Vallone, B. (登録日: 2008-04-15, 公開日: 2009-07-14, 最終更新日: 2023-12-13)

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 (2.1 Å)