8QYI

OleP in complex with lithocholic acid in high salt crystallization conditions

8QYI の概要

• エントリーDOI: 10.2210/pdb8qyi/pdb
• 関連するPDBエントリー: 8QRD
• 分子名称: Cytochrome P-450, PROTOPORPHYRIN IX CONTAINING FE, (3beta,5beta,14beta,17alpha)-3-hydroxycholan-24-oic acid, ... (6 entities in total)
• 機能のキーワード: cytochrome p450, lithocholic acid, complex, oxidoreductase
• 由来する生物種: Streptomyces antibioticus
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 275205.20

構造登録者

Fata, F.,Costanzo, A.,Freda, I.,Gugole, E.,Bulfaro, G.,Barbizzi, L.,Di Renzo, M.,Savino, C.,Vallone, B.,Montemiglio, L.C. (登録日: 2023-10-26, 公開日: 2024-07-03, 最終更新日: 2025-01-22)

主引用文献

Costanzo, A.,Fata, F.,Freda, I.,De Sciscio, M.L.,Gugole, E.,Bulfaro, G.,Di Renzo, M.,Barbizzi, L.,Exertier, C.,Parisi, G.,D'Abramo, M.,Vallone, B.,Savino, C.,Montemiglio, L.C.
Binding of steroid substrates reveals the key to the productive transition of the cytochrome P450 OleP.
Structure, 32:1465-1476.e3, 2024

PubMed Abstract: OleP is a bacterial cytochrome P450 involved in oleandomycin biosynthesis as it catalyzes regioselective epoxidation on macrolide intermediates. OleP has recently been reported to convert lithocholic acid (LCA) into murideoxycholic acid through a highly regioselective reaction and to unspecifically hydroxylate testosterone (TES). Since LCA and TES mainly differ by the substituent group at the C17, here we used X-ray crystallography, equilibrium binding assays, and molecular dynamics simulations to investigate the molecular basis of the diverse reactivity observed with the two steroids. We found that the differences in the structure of TES and LCA affect the capability of these molecules to directly form hydrogen bonds with N-terminal residues of OleP internal helix I. The establishment of these contacts, by promoting the bending of helix I, fosters an efficient trigger of the open-to-closed structural transition that occurs upon substrate binding to OleP and contributes to the selectivity of the subsequent monooxygenation reaction.

PubMed: 38971159
DOI: 10.1016/j.str.2024.06.005

実験手法

X-RAY DIFFRACTION (2.3 Å)