8YIN
Cryo-EM structure of Saccharomyces cerevisiae bc1 complex in YF23694-bound state
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Summary for 8YIN
| Entry DOI | 10.2210/pdb8yin/pdb |
| EMDB information | 39323 |
| Descriptor | COR1 isoform 1, Cytochrome b-c1 complex subunit 10, mitochondrial, (1R)-2-(phosphonooxy)-1-[(tridecanoyloxy)methyl]ethyl pentadecanoate, ... (18 entities in total) |
| Functional Keywords | complex, mitochondria, electron transport, membrane protein |
| Biological source | Saccharomyces cerevisiae (Baker's yeast) More |
| Total number of polymer chains | 20 |
| Total formula weight | 460345.32 |
| Authors | |
| Primary citation | 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 Cited by 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: 39601138DOI: 10.1021/jacs.4c12595 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.74 Å) |
Structure validation
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