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PXD073550-1

PXD073550 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleInhibiting Mrt4-rRNA interaction with fumaramidmycin-based derivatives as an unexploited antifungal strategy-qualitative proteomic
DescriptionThe rise of drug resistance and limitations of current antifungal treatments highlight the urgent need for innovative antifungal strategies. Here we present the development of cis-fumaramidmycin-derived analogues as a novel chemotype inhibiting the interactions of ribosome assembly factor Mrt4 with rRNA to combat fungal infections. Through antifungal screening, we identified a promising lead 20 with strong efficacy against various drug-resistant fungi, including notorious super-fungus Candida auris. A comprehensive approach combining active-and-inactive-based protein profiling (AIBPP), chemical-genetic profiling, and fluorescence polarization revealed that the antifungal activity of 20 is primarily due to selectively inhibiting essential CaMrt4-rRNA interaction by conjointly covalent engaging C96&C189 on CaMrt4 but inactive for HuMrt4-rRNA interaction, thereby disrupting fungal ribosomal assembly. Therapeutic efficacy of 20 in both Galleria mellonella larvae and murine candidiasis models validate this antifungal strategy. Collectively, our studies provide a new and much-need therapeutic strategy to address the rapidly rising burden of drug-resistant fungal infections.
HostingRepositoryPRIDE
AnnounceDate2026-04-27
AnnouncementXMLSubmission_2026-04-26_16:10:57.793.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHu Xiuqi
SpeciesList scientific name: Candida albicans (Yeast); NCBI TaxID: NEWT:5476;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-01-26 00:43:07ID requested
12026-04-26 16:10:58announced
Publication List
10.1038/s41467-026-70226-4;
Cao H, Tu J, Chen J, Chen B, Huang Z, Wang Y, Shen J, Hu X, Bo J, Rao L, Liu Z, Makunga NP, Hameed MS, Su C, Wan J, Chang W, Sheng C, Ren Y, Inhibiting Mrt4-rRNA interaction with fumaramidmycin-based derivatives as an antifungal strategy. Nat Commun, 17(1):(2026) [pubmed]
Keyword List
submitter keyword: ribosome assembly factor, Azole-resistant fungi, protein-RNA interaction,Fumaramidmycin-based derivatives, target identification
Contact List
Jian Wan
contact affiliationState Key Laboratory of Green Pesticide, College of Chemistry, Central China Normal University, Wuhan 430079, China
contact emailjianwan@mail.ccnu.edu.cn
lab head
Hu Xiuqi
contact affiliationcentral china normal university
contact emailhxq981111@126.com
dataset submitter
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Dataset FTP location
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