Inhibition and dynamics of a β-lactamase

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Inhibition and dynamics of a β-lactamase

Type: Doctoral Thesis
Title: Inhibition and dynamics of a β-lactamase
Author: Elings, W.
Issue Date: 2019-11-19
Keywords: BlaC
Clavulanic acid
Protein dynamics
Mycobacterium tuberculosis
Chemical exchange
Simulated evolution
Abstract: BlaC is the β-lactamase of Mycobacterium tuberculosis. We show that it can recover from inhibition by clavulanic acid and that phosphate helps it do so. We also show that in solution, BlaC is a rigid protein on the pico-nanosecond timescale but shows dynamics around the active site on the catalytic timescale. These dynamics become more pronounced upon inhibitor binding. Lastly, we show that two mutations that both provide BlaC with inhibitor resistance have very different effects on the dynamic behaviour.
Promotor: Supervisor: Ubbink M. Co-Supervisor: Wezel G.P. van
Faculty: Science
University: Leiden

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