7R3V

Crystal structure of bovine Cytochrome bc1 in complex with inhibitor CK-2-67.

7R3V の概要

• エントリーDOI: 10.2210/pdb7r3v/pdb
• 分子名称: Cytochrome b-c1 complex subunit 1, mitochondrial, Cytochrome b-c1 complex subunit 9, TETRAETHYLENE GLYCOL, ... (23 entities in total)
• 機能のキーワード: electron transport
• 由来する生物種: Bos taurus (cattle); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 236983.90

構造登録者

Pinthong, N.,Amporndanai, K.,O'Neill, P.M.,Hasnain, S.S.,Antonyuk, S. (登録日: 2022-02-07, 公開日: 2022-08-10, 最終更新日: 2024-01-31)

主引用文献

Amporndanai, K.,Pinthong, N.,O'Neill, P.M.,Hong, W.D.,Amewu, R.K.,Pidathala, C.,Berry, N.G.,Leung, S.C.,Ward, S.A.,Biagini, G.A.,Hasnain, S.S.,Antonyuk, S.V.
Targeting the Ubiquinol-Reduction (Q i ) Site of the Mitochondrial Cytochrome bc 1 Complex for the Development of Next Generation Quinolone Antimalarials.
Biology (Basel), 11:-, 2022

PubMed Abstract: Antimalarials targeting the ubiquinol-oxidation (Q) site of the bc complex, such as atovaquone, have become less effective due to the rapid emergence of resistance linked to point mutations in the Q site. Recent findings showed a series of 2-aryl quinolones mediate inhibitions of this complex by binding to the ubiquinone-reduction (Qi) site, which offers a potential advantage in circumventing drug resistance. Since it is essential to understand how 2-aryl quinolone lead compounds bind within the Qi site, here we describe the co-crystallization and structure elucidation of the bovine cytochrome complex with three different antimalarial 4(1H)-quinolone sub-types, including two 2-aryl quinolone derivatives and a 3-aryl quinolone analogue for comparison. Currently, no structural information is available for cytochrome . Our crystallographic studies have enabled comparison of an in-silico homology docking model of with the mammalian's equivalent, enabling an examination of how binding compares for the 2- versus 3-aryl analogues. Based on crystallographic and computational modeling, key differences in human and Q sites have been mapped that provide new insights that can be exploited for the development of next-generation antimalarials with greater selective inhibitory activity against the parasite with improved antimalarial properties.

PubMed: 35892964
DOI: 10.3390/biology11081109

実験手法

X-RAY DIFFRACTION (3.2 Å)