- EMDB-60320: Cryo-EM structure of Metyltetraprole-bound porcine bc1 complex -
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基本情報
登録情報
データベース: EMDB / ID: EMD-60320
タイトル
Cryo-EM structure of Metyltetraprole-bound porcine bc1 complex
マップデータ
試料
複合体: Cryo-EM structure of Metyltetraprole-bound porcine bc1 complex
タンパク質・ペプチド: x 11種
リガンド: x 6種
キーワード
Metyltetraprole / Inhibitor / Complex / PROTEIN BINDING
機能・相同性
機能・相同性情報
Complex III assembly / subthalamus development / pons development / cerebellar Purkinje cell layer development / pyramidal neuron development / thalamus development / Respiratory electron transport / Mitochondrial protein degradation / respiratory chain complex III / quinol-cytochrome-c reductase ...Complex III assembly / subthalamus development / pons development / cerebellar Purkinje cell layer development / pyramidal neuron development / thalamus development / Respiratory electron transport / Mitochondrial protein degradation / respiratory chain complex III / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / midbrain development / hypothalamus development / mitochondrial electron transport, ubiquinol to cytochrome c / hippocampus development / metalloendopeptidase activity / 2 iron, 2 sulfur cluster binding / electron transfer activity / mitochondrial inner membrane / heme binding / mitochondrion / proteolysis / membrane / metal ion binding 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
中国
引用
ジャーナル: J Am Chem Soc / 年: 2024 タイトル: Cryo-EM Structures Reveal the Unique Binding Modes of Metyltetraprole in Yeast and Porcine Cytochrome Complex Enabling Rational Design of Inhibitors. 著者: Yu-Xia Wang / Ying Ye / Zhi-Wen Li / Guang-Rui Cui / Xing-Xing Shi / Ying Dong / Jia-Jia Jiang / Jia-Yue Sun / Ze-Wei Guan / Nan Zhang / Qiong-You Wu / Fan Wang / Xiao-Lei Zhu / Guang-Fu Yang / 要旨: 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 ...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.