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Structure paper

TitleCryo-EM structure of the yeast Saccharomyces cerevisiae SDH provides a template for eco-friendly fungicide discovery.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 8936, Year 2025
Publish dateOct 8, 2025
AuthorsZhi-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 /
PubMed AbstractSuccinate 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.
External linksNat Commun / PubMed:41062466 / PubMed Central
MethodsEM (single particle)
Resolution3.06 - 3.36 Å
Structure data

62490

9kps

EMDB-62490, PDB-9kps:
Cryo-EM structure of Saccharomyces cerevisiae Mitochondrial Respiratory Complex II
Method: EM (single particle) / Resolution: 3.36 Å

62491

9kpt

EMDB-62491, PDB-9kpt:
Cryo-EM structure of Saccharomyces cerevisiae Mitochondrial Respiratory Complex II in UQ1-bound state
Method: EM (single particle) / Resolution: 3.25 Å

62495

9kq3

EMDB-62495, PDB-9kq3:
Cryo-EM structure of Saccharomyces cerevisiae Mitochondrial Respiratory Complex II in pydiflumetofen-bound state
Method: EM (single particle) / Resolution: 3.23 Å

63115

9lig

EMDB-63115, PDB-9lig:
Cryo-EM structure of Saccharomyces cerevisiae Mitochondrial Respiratory Complex II in Y19315-bound state
Method: EM (single particle) / Resolution: 3.06 Å

Chemicals

ChemComp-FAD:
FLAVIN-ADENINE DINUCLEOTIDE / FAD*YM

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-SF4:
IRON/SULFUR CLUSTER

ChemComp-F3S:
FE3-S4 CLUSTER

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM

ChemComp-UQ1:
UBIQUINONE-1

PDB-1ee4:
CRYSTAL STRUCTURE OF YEAST KARYOPHERIN (IMPORTIN) ALPHA IN A COMPLEX WITH A C-MYC NLS PEPTIDE

PDB-1ekv:
HUMAN BRANCHED CHAIN AMINO ACID AMINOTRANSFERASE (MITOCHONDRIAL): THREE DIMENSIONAL STRUCTURE OF ENZYME INACTIVATED BY TRIS BOUND TO THE PYRIDOXAL-5'-PHOSPHATE ON ONE END AND ACTIVE SITE LYS202 NZ ON THE OTHER.

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsMEMBRANE PROTEIN / Complex / mitochondria / ELECTRON TRANSPORT

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