Evolution acts via mutations in amino acid sequences. Substitution of essential amino acids leads to a nonfunctional protein. Thus, the number of essential residues is limited by evolutionary... Show moreEvolution acts via mutations in amino acid sequences. Substitution of essential amino acids leads to a nonfunctional protein. Thus, the number of essential residues is limited by evolutionary pressure. The roles of all non-catalytic essential residues in class A β-lactamases are described with a large-scale experiments, as well as specific functions of a few residues. The results show that residues close to the active site and farther away have different reasons for being essential. Show less
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... Show moreBlaC 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. Show less
