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Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling.

ABSTRACT: Thermal stabilization of proteins after ligand binding provides an efficient means to assess the binding of small molecules to proteins. We show here that in combination with quantitative mass spectrometry, the approach allows for the systematic survey of protein engagement by cellular metabolites and drugs. We profiled the targets of the drugs methotrexate and (S)-crizotinib and the metabolite 2'3'-cGAMP in intact cells and identified the 2'3'-cGAMP cognate transmembrane receptor STING, involved in immune signaling.

SUBMITTER: Huber KV

PROVIDER: S-EPMC4629415 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling.

Huber Kilian V M KV Olek Karin M KM Müller André C AC Tan Chris Soon Heng CS Bennett Keiryn L KL Colinge Jacques J Superti-Furga Giulio G

Nature methods 20150921 11

Thermal stabilization of proteins after ligand binding provides an efficient means to assess the binding of small molecules to proteins. We show here that in combination with quantitative mass spectrometry, the approach allows for the systematic survey of protein engagement by cellular metabolites and drugs. We profiled the targets of the drugs methotrexate and (S)-crizotinib and the metabolite 2'3'-cGAMP in intact cells and identified the 2'3'-cGAMP cognate transmembrane receptor STING, involve ...[more]

PMID: 26389571

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