PXD073550

PXD073550 is an original dataset announced via ProteomeXchange.

Title	Inhibiting Mrt4-rRNA interaction with fumaramidmycin-based derivatives as an unexploited antifungal strategy-qualitative proteomic
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-26_16:10:57.793.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hu Xiuqi
SpeciesList	scientific name: Candida albicans (Yeast); NCBI TaxID: NEWT:5476;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-26 00:43:07	ID requested
⏵ 1	2026-04-26 16:10:58	announced

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]

submitter keyword: ribosome assembly factor, Azole-resistant fungi, protein-RNA interaction,Fumaramidmycin-based derivatives, target identification

Jian Wan
contact affiliation	State Key Laboratory of Green Pesticide, College of Chemistry, Central China Normal University, Wuhan 430079, China
contact email	jianwan@mail.ccnu.edu.cn
lab head
Hu Xiuqi
contact affiliation	central china normal university
contact email	hxq981111@126.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073550

PRIDE project URI

• PRIDE
  1. PXD073550
     1. Label: PRIDE project
     2. Name: Inhibiting Mrt4-rRNA interaction with fumaramidmycin-based derivatives as an unexploited antifungal strategy-qualitative proteomic