PXD064801

PXD064801 is an original dataset announced via ProteomeXchange.

Title	Rational Design of Benzo-Dioxygenated FabH Inhibitors Unveiled by Proteomic Profiling: Broad-Spectrum Antibacterial Activity and In Vivo Therapeutic Efficacy
Description	The global escalation of antibiotic-resistant bacterial infections poses a life-threatening challenge to public health, necessitating the urgent development of innovative antibiotics targeting unexploited metabolic vulnerabilities. Through rational design, we developed a series of benzo-dioxygenated FabH inhibitors targeting the bacterial fatty acid biosynthesis pathway. Guided by active-site analysis and pharmacophore-guided optimization, we engineered a Y-shaped scaffold that achieved nanomolar inhibition of FabH (IC50 = 1.90 µM). The lead compound F35 showed broad-spectrum efficacy with MIC values as low as 1.56 µg/mL against Gram-negative and Gram-positive pathogens, outperforming Kanamycin B. Structural analysis revealed key interactions between FabH conserved residues and fluorine-mediated halogen bonding. In vivo assay, F35 accelerated wound closure in S. aureus-infected rodents, demonstrating a favorable biocompatibility. Our study establishes a convergence paradigm that integrates structure design, chemoproteomic identification, and therapeutic development for antibiotics, providing a strategic blueprint to combat multidrug resistance via precision targeting of metabolic chokepoints in bacterial pathogens.
HostingRepository	iProX
AnnounceDate	2025-06-10
AnnouncementXML	Submission_2026-06-01_19:24:24.734.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rui Wang
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-09 23:35:50	ID requested
⏵ 1	2026-06-01 19:24:25	announced

Dataset with its publication pending

submitter keyword: LiP-MS, Benzo-Dioxygenated FabH Inhibitors

Rui Wang
contact affiliation	shenzhen bay laboratory
contact email	wangrui@szbl.ac.cn
lab head
Rui Wang
contact affiliation	shenzhen bay laboratory
contact email	wangrui@szbl.ac.cn
dataset submitter

iProX dataset URI