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Biochem J ; 476(21): 3125-3139, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31488574

ABSTRACT

CoaBC, part of the vital coenzyme A biosynthetic pathway in bacteria, has recently been validated as a promising antimicrobial target. In this work, we employed native ion mobility-mass spectrometry to gain structural insights into the phosphopantothenoylcysteine synthetase domain of E. coli CoaBC. Moreover, native mass spectrometry was validated as a screening tool to identify novel inhibitors of this enzyme, highlighting the utility and versatility of this technique both for structural biology and for drug discovery.


Subject(s)
Carboxy-Lyases/chemistry , Drug Evaluation, Preclinical/methods , Escherichia coli Proteins/chemistry , Escherichia coli/enzymology , Mass Spectrometry/methods , Multienzyme Complexes/chemistry , Peptide Synthases/chemistry , Carboxy-Lyases/antagonists & inhibitors , Carboxy-Lyases/metabolism , Dimerization , Enzyme Inhibitors/chemistry , Escherichia coli/chemistry , Escherichia coli/drug effects , Escherichia coli/genetics , Escherichia coli Proteins/antagonists & inhibitors , Escherichia coli Proteins/metabolism , Kinetics , Multienzyme Complexes/antagonists & inhibitors , Multienzyme Complexes/metabolism , Peptide Synthases/antagonists & inhibitors , Peptide Synthases/metabolism , Protein Domains
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