PXD043275 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Activity-Based Protein Profiling in Methicillin-Resistant Staphylococcus aureus Reveals Broad Reactivity of a Carmofur-Derived Probe |
Description | Activity-based protein profiling is a powerful chemoproteomic technique to detect active enzymes and identify targets and off-targets of drugs. Here, we report on the use of a carmofur-based activity-based probe to identify biologically relevant enzymes in the bacterial pathogen Staphylococcus aureus. Carmofur is an anti-neoplastic prodrug with antimicrobial activity that is related to 5-fluorouracil. The carmofur-probe was originally designed to target human acid ceramidase, a member of the Ntn hydrolase family with an active-site cysteine nucleophile. Here, we first profiled the targets of a fluorescent carmofur-probe in live S. aureus under biofilm-promoting conditions and in liquid culture, before proceeding to target identification by liquid chromatograpy/mass spectrometry. Treatment with a carmofur-biotin probe led to enrichment of 21 enzymes from diverse families awaiting further characterization, including the Ntn hydrolase-related IMP cyclohydrolase PurH. However, the probe preferentially labelled serine hydrolases, thus displaying a reactivity profile similar to carbamates. Our results suggest that the electrophilic N-carbamoyl-5-fluorouracil scaffold could potentially be optimized to achieve selectivity towards diverse enzyme families. The observed promiscuous reactivity profile suggests that the clinical use of carmofur presumably leads to inactivation of a number human and microbial enzymes that could lead to side-effects or even contribute to therapeutic efficacy. |
HostingRepository | PRIDE |
AnnounceDate | 2024-01-29 |
AnnouncementXML | Submission_2024-01-29_07:47:18.709.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Md Jalal Uddin |
SpeciesList | scientific name: Bacteria; NCBI TaxID: NCBITaxon:2; scientific name: Staphylococcus aureus; NCBI TaxID: 1280; |
ModificationList | No PTMs are included in the dataset |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-06-25 05:00:34 | ID requested | |
⏵ 1 | 2024-01-29 07:47:19 | announced | |
Publication List
Keyword List
submitter keyword: biofilm, activity-based protein profiling , carmofur,S. aureus |
Contact List
Christian S. Lentz |
contact affiliation | Assoc. Prof. Dr. Christian S. Lentz Associate Professor, Department of Medical Biology, UiT- The Arctic University of Norway, 9019 Tromsø, Norway |
contact email | christian.s.lentz@uit.no |
lab head | |
Md Jalal Uddin |
contact affiliation | UiT The Arctic University of Norway |
contact email | jalal.uddin@uit.no |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD043275
- Label: PRIDE project
- Name: Activity-Based Protein Profiling in Methicillin-Resistant Staphylococcus aureus Reveals Broad Reactivity of a Carmofur-Derived Probe