Eric Girard, Pedro Lopes, Michael Spoerner, Anne-Claire Dhaussy, Thierry Prangé, Hans Robert Kalbitzer, Nathalie Colloc'h
In this work, we experimentally investigate the potency of high pressure to drive a protein toward an excited state where an inhibitor targeted for this state can bind. Ras proteins are small GTPases cycling between active GTP-bound and inactive GDP-bound states. Various states of GTP-bound Ras in active conformation coexist in solution, amongst them, state 2 which binds to effectors, and state 1, weakly populated at ambient conditions, which has a low affinity for effectors. Zn2+-cyclen is an allosteric inhibitor of Ras protein, designed to bind specifically to the state 1...
April 22, 2024: Chemistry: a European Journal