The G132S Mutation Enhances the Resistance of <i>Mycobacterium tuberculosis</i> β-Lactamase against Sulbactam
Ilona van Alen, Aleksandra Chikunova, Adil A. Safeer, Misbha Ud Din Ahmad, Anastassis Perrakis, Marcellus Ubbink
Abstract
conformation and the side chain of Ser104 to be rotated toward the sulbactam adduct with which it forms a hydrogen bond not present in the wild-type enzyme. The gatekeeper residue Ile105 also moves. These changes in the entrance of the active site can explain the decreased affinity of G132S BlaC for both substrates and sulbactam. Our results show that BlaC can easily acquire a reduced sensitivity for sulbactam, with a single-amino acid mutation, which could hinder the use of combination therapies.
Topics & Concepts
SulbactamMicrobiologyChemistrySaturated mutagenesisMycobacterium tuberculosisBiochemistryAntibioticsAntibiotic resistanceBiologyTuberculosisMutantMedicineImipenemGenePathologyAntibiotic Resistance in BacteriaTuberculosis Research and EpidemiologyCancer therapeutics and mechanisms