6L39

Cytochrome P450 107G1 (RapN)

6L39 の概要

• エントリーDOI: 10.2210/pdb6l39/pdb
• 分子名称: Cytochrome P450, PROTOPORPHYRIN IX CONTAINING FE, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• 機能のキーワード: cytochrome p450, oxidoreductase
• 由来する生物種: Streptomyces rapamycinicus (strain ATCC 29253 / DSM 41530 / NRRL 5491 / AYB-994)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91904.91

構造登録者

Kim, V.C.,Kim, D.H.,Lim, Y.R.,Lee, I.H.,Lee, J.H.,Kang, L.W. (登録日: 2019-10-10, 公開日: 2020-09-16, 最終更新日: 2023-11-22)

主引用文献

Kim, V.,Lim, Y.R.,Lee, I.,Lee, J.H.,Han, S.,Pham, T.V.,Kim, H.,Lee, R.,Kang, L.W.,Kim, D.
Structural insights into CYP107G1 from rapamycin-producing Streptomyces rapamycinicus.
Arch.Biochem.Biophys., 692:108544-108544, 2020

PubMed Abstract: Rapamycin is a clinically important macrolide agent with immunosuppressant and antiproliferative properties, produced by the actinobacterium, Streptomyces rapamycinicus. Two cytochrome P450 enzymes are involved in the biosynthesis of rapamycin. CYP107G1 and CYP122A2 catalyze the oxidation reactions of C27 and C9 of pre-rapamycin, respectively. To understand the structural and biochemical features of P450 enzymes in rapamycin biosynthesis, the CYP107G1 and CYP122A2 genes were cloned, their recombinant proteins were expressed in Escherichia coli, and the purified enzymes were characterized. Both enzymes displayed low spin states in the absolute spectra of ferric forms, and the titrations with rapamycin induced type I spectral changes with K values of 4.4 ± 0.4 and 3.0 ± 0.3 μM for CYP107G1 and CYP122A2, respectively. The X-ray crystal structures of CYP107G1 and its co-crystal complex with everolimus, a clinical rapamycin derivative, were determined at resolutions of 2.9 and 3.0 Å, respectively. The overall structure of CYP107G1 adopts the canonical scaffold of cytochrome P450 and possesses large substrate pocket. The distal face of the heme group is exposed to solvents to accommodate macrolide access. When the structure of the everolimus-bound CYP107G1 complex (CYP107G1-Eve) was compared to that of the ligand-free CYP107G1 form, no significant conformational change was observed. Hence, CYP107G1 has a relatively rigid structure with versatile loops to accommodate a bulky substrate. The everolimus molecule is bound to the substrate-binding pocket in the shape of a squeezed donut, and its elongated structure is bound perpendicular to a planar heme plane and I-helix.

PubMed: 32822639
DOI: 10.1016/j.abb.2020.108544

実験手法

X-RAY DIFFRACTION (2.97 Å)