Two β-Lactamase Variants with Reduced Clavulanic Acid Inhibition Display Different Millisecond Dynamics
Wouter Elings, Aleksandra Chikunova, Danny B. van Zanten, Ralphe Drenth, Misbha Ud Din Ahmad, Anneloes Blok, Monika Timmer, Anastassis Perrakis, Marcellus Ubbink
Abstract
-conformation. The crystal structure suggests multiple conformations for several side chains (e.g., Ser104 and Ser130) and a short loop (positions 214 to 216). In the K234R mutant, the active-site dynamics are significantly diminished with respect to the wild-type enzyme. These results show that multiple evolutionary routes are available to increase inhibitor resistance in BlaC and that active-site dynamics on the millisecond time scale are not required for catalytic function.
Topics & Concepts
Clavulanic acidEscherichia coliMycobacterium tuberculosisMicrobiologyEnzymeBeta-Lactamase InhibitorsMutationBiologyChemistryTuberculosisAntibioticsGeneticsBiochemistryGeneAmoxicillinMedicinePathologyAntibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyEnzyme Structure and Function