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PXD058002

PXD058002 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIntegrated Phenotypic and Activity-Based Profiling of Electrophilic Fragments Reveals New Targets for Antibiotics Development
DescriptionThe emergence of antibiotic resistance necessitates the discovery of novel bacterial targets and antimicrobial agents. Here, we present a bacterial target discovery framework that integrates phenotypic screening of cysteine-reactive fragments with competitive activity-based protein profiling to map and functionally characterize the targets of screening hits. Using this approach, we identify FabH -ketoacyl synthase and MiaA tRNA prenyltransferase as primary targets of a hit fragment, 10-F05, that confer bacterial stress resistance and virulence in Shigella flexneri. Mechanistic investigations elucidate that covalent C112 modification in FabH, an enzyme involved in bacterial fatty acid synthesis, results in its inactivation and consequent growth inhibition. We further demonstrate that irreversible C273 modification at the MiaA RNA-protein interaction interface abrogates substrate tRNA binding, attenuating resistance and virulence through decreased translational accuracy. Our findings underscore the efficacy of integrating phenotypic and activity-based profiling of electrophilic fragments to accelerate the identification and pharmacologic validation of new therapeutic targets.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-07_05:01:37.434.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMikail Abbasov
SpeciesList scientific name: Shigella flexneri S5644; NCBI TaxID: 1210043; scientific name: Bacteria; NCBI TaxID: NCBITaxon:2;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-11-18 11:32:56ID requested
12025-05-07 05:01:38announced
Publication List
10.1016/j.chembiol.2025.02.001;
Jin Y, Jana S, Abbasov ME, Lin H, Antibiotic target discovery by integrated phenotypic and activity-based profiling of electrophilic fragments. Cell Chem Biol, 32(3):434-448.e9(2025) [pubmed]
Keyword List
submitter keyword: Phenotypic screening
covalent inhibitor
antibiotics
activity-based protein profiling
FabH
MiaA
PdxY
Contact List
Mikail E. Abbasov
contact affiliationCornell University
contact emailmikail.abbasov@cornell.edu
lab head
Mikail Abbasov
contact affiliationCornell University
contact emailabbasovgroupcornell@gmail.com
dataset submitter
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Dataset FTP location
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