Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.

ABSTRACT: The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the con

SUBMITTER: Maciag JJ 

PROVIDER: S-EPMC5068305 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature