Conformational selection and adaptation to ligand binding in T4 lysozyme cavity mutants.

ABSTRACT: The studies presented here explore the relationship between protein packing and molecular flexibility using ligand-binding cavity mutants of T4 lysozyme. Although previously reported crystal structures of the mutants investigated show single conformations that are similar to the WT protein, site-directed spin labeling in solution reveals additional conformational substates in equilibrium exchange with a WT-like population. Remarkably, binding of ligands, including the general anesthetic halothane shifts the population to the WT-like state, consistent with a conformational selection model of ligand binding, but structural adaptation to the ligand is also apparent in one mutant. Distance mapping with double electron-electron resonance spectroscopy and the absence of ligand binding suggest th

SUBMITTER: Lopez CJ 

PROVIDER: S-EPMC3832024 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature