8ZOW

Cryo-EM structure of Metyltetraprole-bound porcine bc1 complex

これはPDB形式変換不可エントリーです。

8ZOW の概要

• エントリーDOI: 10.2210/pdb8zow/pdb
• EMDBエントリー: 60320
• 分子名称: Cytochrome b, Cytochrome b-c1 complex subunit 10, Cytochrome b-c1 complex subunit Rieske, mitochondrial, ... (17 entities in total)
• 機能のキーワード: metyltetraprole, inhibitor, complex, protein binding
• 由来する生物種: Sus scrofa (pig); 詳細
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 479309.86

構造登録者

Wang, Y.X.,Sun, J.Y.,Cui, G.R.,Yang, G.F. (登録日: 2024-05-29, 公開日: 2024-12-25)

主引用文献

Wang, Y.X.,Ye, Y.,Li, Z.W.,Cui, G.R.,Shi, X.X.,Dong, Y.,Jiang, J.J.,Sun, J.Y.,Guan, Z.W.,Zhang, N.,Wu, Q.Y.,Wang, F.,Zhu, X.L.,Yang, G.F.
Cryo-EM Structures Reveal the Unique Binding Modes of Metyltetraprole in Yeast and Porcine Cytochrome bc 1 Complex Enabling Rational Design of Inhibitors.
J.Am.Chem.Soc., 146:33903-33913, 2024

PubMed Abstract: Cytochrome (complex III) represents a significant target for the discovery of both drugs and fungicides. Metyltetraprole (MET) is commonly classified as a quinone site inhibitor (QI) that combats the G143A mutated isolate, which confers high resistance to strobilurin fungicides such as pyraclostrobin (PYR). The binding mode and antiresistance mechanism of MET remain unclear. Here, we determined the high-resolution structures of inhibitor-bound complex III (MET, 2.52 Å; PYR, 2.42 Å) and inhibitor-bound porcine complex III (MET, 2.53 Å; PYR, 2,37 Å) by cryo-electron microscopy. The distinct binding modes of MET and PYR were observed for the first time. Notably, the MET exhibited different binding modes in the two species. In , the binding site of MET was the same as PYR, serving as a -type inhibitor of the Q site. However, in porcine, MET acted as a dual-target inhibitor of both Q and Q. Based on the structural insights, a novel inhibitor (YF23694) was discovered and demonstrated excellent fungicidal activity against downy mildew and powdery mildew fungi. This work provides a new starting point for the design of the next generation of inhibitors to overcome the resistance.

PubMed: 39601138
DOI: 10.1021/jacs.4c12595

実験手法

ELECTRON MICROSCOPY (2.53 Å)