Hydrogen exchange and ligand binding: ligand-dependent and ligand-independent protection in the Src SH3 domain.

ABSTRACT: Amide hydrogen-deuterium exchange has proven to be a powerful tool for detecting and characterizing high-energy conformations in protein ensembles. Since interactions with ligands can modulate these high-energy conformations, hydrogen exchange appears to be an ideal experimental probe of the physical mechanisms underlying processes like allosteric regulation. The chemical mechanism of hydrogen exchange, however, can complicate such studies. Here, we examine hydrogen exchange rates in a simple model system, the c-Src SH3 domain interacting with a short peptide ligand. Addition of ligand slows the rates of hydrogen exchange at nearly every amide for which we can obtain data. Careful analysis, however, reveals that this slowing is due primarily to a reduction in the population of free protein

SUBMITTER: Wildes D 

PROVIDER: S-EPMC2253332 | biostudies-literature | 2005 Jan

REPOSITORIES: biostudies-literature