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9KPT

Cryo-EM structure of Saccharomyces cerevisiae Mitochondrial Respiratory Complex II in UQ1-bound state

Summary for 9KPT
Entry DOI10.2210/pdb9kpt/pdb
EMDB information62491
DescriptorSuccinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial, ... (10 entities in total)
Functional Keywordscomplex, mitochondria, electron transport, membrane protein
Biological sourceSaccharomyces cerevisiae (brewer's yeast)
More
Total number of polymer chains4
Total formula weight125912.99
Authors
Li, Z.W.,Ye, Y.,Yang, G.F. (deposition date: 2024-11-24, release date: 2025-09-03, Last modification date: 2025-10-22)
Primary citationLi, Z.W.,Huang, Y.H.,Wei, G.,Lu, Z.W.,Wang, Y.X.,Cui, G.R.,Wang, J.Y.,Yu, X.H.,Fu, Y.X.,Fan, E.D.,Wu, Q.Y.,Zhu, X.L.,Ye, Y.,Yang, G.F.
Cryo-EM structure of the yeast Saccharomyces cerevisiae SDH provides a template for eco-friendly fungicide discovery.
Nat Commun, 16:8936-8936, 2025
Cited by
PubMed Abstract: Succinate dehydrogenase (SDH) is a key fungicidal target, but rational inhibitors design has been impeded by the lack of fungal SDH structure. Here, we show the cryo-EM structure of SDH from Saccharomyces cerevisiae (ScSDH) in apo (3.36 Å) and ubiquinone-1-bound (3.25 Å) states, revealing subunits architecture and quinone-binding sites (Q). ScSDH is classified as a heme-deficient type-D SDH, utilizing conserved redox centers (FAD, [2Fe-2S], [4Fe-4S] and [3Fe-4S] clusters) for electron transfer. A 3.23 Å structure with pydiflumetofen (PYD) identified critical interactions, including hydrogen bonds with Trp_SDHB194 and Tyr_SDHD120, and a cation-π interaction with Arg_SDHC97. Leveraging this, we designed a SDH inhibitor E8 (enprocymid), exhibiting significant fungicidal activity (K = 0.019 μM) and reduced zebrafish toxicity (LC (96 h) = 1.01 mg a.i./L). This study elucidates the structure of fungal SDH and demonstrates the potential of ScSDH for rational design of next-generation fungicides, addressing fungal resistance and environmental toxicity in agriculture.
PubMed: 41062466
DOI: 10.1038/s41467-025-64001-0
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.25 Å)
Structure validation

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