MassIVE MSV000088127

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An Allosteric Inhibitor of Bacterial Hsp70 Chaperone Potentiates Antibiotics and Combats Resistance

Description

In the pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), DnaK and its cofactors are proposed antimycobacterial targets. Here, we discover that a repurposed drug called telaprevir is able to allosterically inhibit the ATPase activity of DnaK from several organisms, and prevents chaperone function by mimicking peptide substrates. We designed a photoreactive probe that binds to the same region of DnaK as telaprevir. After crosslinking the probe, mass spectrometry was used to identify the site of interaction. Based on crosslink spectral matches (CSMs), eighty percent of the modified peptides were located in the beta-sandwich domain spanning from Glu398 to Ser409. The most highly represented modified residue was Asn406, followed by Glu398 and Asp405, all of which are present in the peptide binding cleft. [doi:10.25345/C5DC35] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: crosslinking

Contact

Principal Investigators:
(in alphabetical order)
Beatrix Ueberheide, NYU Grossman School of Medicine, USA
Submitting User: Trixi
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Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

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Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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