Warintra Pitsawong

TL;DR: Applying a suite of nuclear magnetic resonance, crystallography, and stopped-flow techniques to an enzyme designed for an elementary proton transfer reaction, it is shown how directed evolution gradually altered the conformational ensemble of the protein scaffold to populate a narrow, highly active conformationalsemble and accelerate this transformation by nearly nine orders of magnitude.

TL;DR: NMR measurements and X-ray crystallography show that wild-type SHP2 dynamically exchanges between a closed inactive conformation and an open activated form and that the oncogenic E76K mutation shifts the equilibrium to the open state, which is reversed by binding of the allosteric inhibitor SHP099.

TL;DR: The data suggest that a competent reductive half-reaction requires a side chain at position 169 that is able to form an H-bond within the ES complex, and that the precise position and geometry of the Thr169 side chain are required for intermediate stabilization.

TL;DR: Simple transient kinetics in both the reductive and oxidative half-reactions that help to explain the broad substrate repertoire of NR are demonstrated.

TL;DR: This work investigates whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Aurora A and proposes a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors.