Inhibition and dynamics of a β-lactamase

Elings, W. (2019)

Doctoral Thesis

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.

• BlaC
• Inhibition
• Clavulanic acid
• NMR
• Protein dynamics
• Mycobacterium tuberculosis
• Chemical exchange
• Simulated evolution

• All authors: Elings, W.
• Supervisor: Ubbink, M.
• Co-supervisor: Wezel, G.P. van
• Committee: Overkleeft, H.S.; Meijer, A.H.; Hagedoorn, P.-L.; Hansen, D.F.
• Qualification: Doctor (dr.)
• Awarding Institution: LIC / Macromolecular Biochemistry, Science, Leiden
• Date: 2019-11-19