National Natural Science Foundation of China (NSFC)
中国
引用
ジャーナル: Nat Commun / 年: 2025 タイトル: Cryo-EM structure of the yeast Saccharomyces cerevisiae SDH provides a template for eco-friendly fungicide discovery. 著者: Zhi-Wen Li / Yuan-Hui Huang / Ge Wei / Zong-Wei Lu / Yu-Xia Wang / Guang-Rui Cui / Jun-Ya Wang / Xin-He Yu / Yi-Xuan Fu / Er-Di Fan / Qiong-You Wu / Xiao-Lei Zhu / Ying Ye / Guang-Fu Yang / 要旨: 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 ...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.
名称: Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial タイプ: protein_or_peptide / ID: 1 詳細: The sample used was sourced from Saccharomyces cerevisiae (Tax ID: 4932), strain Redstar, with the GenBank ID in the SGD database being JRIL00000000. Sequence reference for Saccharomyces ...詳細: The sample used was sourced from Saccharomyces cerevisiae (Tax ID: 4932), strain Redstar, with the GenBank ID in the SGD database being JRIL00000000. Sequence reference for Saccharomyces cerevisiae strain RedStar is not available in UniProt at the time of biocuration. Current sequence reference is from UniProt ID Q00711. コピー数: 1 / 光学異性体: LEVO / EC番号: succinate dehydrogenase
名称: Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial タイプ: protein_or_peptide / ID: 2 詳細: The sample used was sourced from Saccharomyces cerevisiae (Tax ID: 4932), strain Redstar, with the GenBank ID in the SGD database being JRIL00000000. Sequence reference for Saccharomyces ...詳細: The sample used was sourced from Saccharomyces cerevisiae (Tax ID: 4932), strain Redstar, with the GenBank ID in the SGD database being JRIL00000000. Sequence reference for Saccharomyces cerevisiae strain RedStar is not available in UniProt at the time of biocuration. Current sequence reference is from UniProt ID P21801. コピー数: 1 / 光学異性体: LEVO / EC番号: succinate dehydrogenase
名称: Sdh3p / タイプ: protein_or_peptide / ID: 3 詳細: The sample used was sourced from Saccharomyces cerevisiae (Tax ID: 4932), strain Redstar, with the GenBank ID in the SGD database being JRIL00000000. Sequence reference for Saccharomyces ...詳細: The sample used was sourced from Saccharomyces cerevisiae (Tax ID: 4932), strain Redstar, with the GenBank ID in the SGD database being JRIL00000000. Sequence reference for Saccharomyces cerevisiae strain RedStar is not available in UniProt at the time of biocuration. Current sequence reference is from UniProt ID C7GVH5. コピー数: 1 / 光学異性体: LEVO
分子 #4: Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, ...
分子
名称: Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial タイプ: protein_or_peptide / ID: 4 詳細: The sample used was sourced from Saccharomyces cerevisiae (Tax ID: 4932), strain Redstar, with the GenBank ID in the SGD database being JRIL00000000. Sequence reference for Saccharomyces ...詳細: The sample used was sourced from Saccharomyces cerevisiae (Tax ID: 4932), strain Redstar, with the GenBank ID in the SGD database being JRIL00000000. Sequence reference for Saccharomyces cerevisiae strain RedStar is not available in UniProt at the time of biocuration. Current sequence reference is from UniProt ID P37298. コピー数: 1 / 光学異性体: LEVO