The designability of protein switches by chemical rescue of structure: mechanisms of inactivation and reactivation.

ABSTRACT: The ability to selectively activate function of particular proteins via pharmacological agents is a longstanding goal in chemical biology. Recently, we reported an approach for designing a de novo allosteric effector site directly into the catalytic domain of an enzyme. This approach is distinct from traditional chemical rescue of enzymes in that it relies on disruption and restoration of structure, rather than active site chemistry, as a means to achieve modulate function. However, rationally identifying analogous de novo binding sites in other enzymes represents a key challenge for extending this approach to introduce allosteric control into other enzymes. Here we show that mutation sites leading to protein inactivation via tryptophan-to-glycine substitution and allowing (partial) reacti

SUBMITTER: Xia Y 

PROVIDER: S-EPMC3919134 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature