β-Lactamase of Mycobacterium tuberculosis Shows Dynamics in the Active Site That Increase upon Inhibitor Binding.

ABSTRACT: The Mycobacterium tuberculosis β-lactamase BlaC is a broad-spectrum β-lactamase that can convert a range of β-lactam antibiotics. Enzymes with low specificity are expected to exhibit active-site flexibility. To probe the motions in BlaC, we studied the dynamic behavior in solution using nuclear magnetic resonance (NMR) spectroscopy. ¹⁵N relaxation experiments show that BlaC is mostly rigid on the pico- to nanosecond timescale. Saturation transfer experiments indicate that also on the high-millisecond timescale BlaC is not dynamic. Using relaxation dispersion experiments, clear evidence was obtained for dynamics in the low-millisecond range, with an exchange rate of ca. 860 s^-1 The dynamic amide groups are localized in the active site. Upon formation of an adduc

SUBMITTER: Elings W 

PROVIDER: S-EPMC7038250 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature