8zos | pdb_00008zos

Cryo-EM structure of pyraclostrobin-bound porcine bc1 complex

spinqualitylabelsall models 8zos, resolution 2.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8zos is a 20 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.37Å Ligands: A1D6K, CDL, FES, HEC, HEM, PEE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F1SDI2_PIG Publication Abstract from PubMed Cytochrome bc(1) (complex III) represents a significant target for the discovery of both drugs and fungicides. Metyltetraprole (MET) is commonly classified as a quinone site inhibitor (Q(o)I) 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 S. cerevisiae complex III (MET, 2.52 A; PYR, 2.42 A) and inhibitor-bound porcine complex III (MET, 2.53 A; PYR, 2,37 A) 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 S. cerevisiae, the binding site of MET was the same as PYR, serving as a Pm-type inhibitor of the Q(o) site. However, in porcine, MET acted as a dual-target inhibitor of both Q(o) and Q(i). 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. Cryo-EM Structures Reveal the Unique Binding Modes of Metyltetraprole in Yeast and Porcine Cytochrome bc(1) Complex Enabling Rational Design of Inhibitors.,Wang YX, Ye Y, Li ZW, Cui GR, Shi XX, Dong Y, Jiang JJ, Sun JY, Guan ZW, Zhang N, Wu QY, Wang F, Zhu XL, Yang GF J Am Chem Soc. 2024 Dec 11;146(49):33903-33913. doi: 10.1021/jacs.4c12595. Epub , 2024 Nov 27. PMID:39601138 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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