Mechanism of protein kinetic stabilization by engineered disulfide crosslinks.

ABSTRACT: The impact of disulfide bonds on protein stability goes beyond simple equilibrium thermodynamics effects associated with the conformational entropy of the unfolded state. Indeed, disulfide crosslinks may play a role in the prevention of dysfunctional association and strongly affect the rates of irreversible enzyme inactivation, highly relevant in biotechnological applications. While these kinetic-stability effects remain poorly understood, by analogy with proposed mechanisms for processes of protein aggregation and fibrillogenesis, we propose that they may be determined by the properties of sparsely-populated, partially-unfolded intermediates. Here we report the successful design, on the basis of high temperature molecular-dynamics simulations, of six thermodynamically and kinetically stab

SUBMITTER: Sanchez-Romero I 

PROVIDER: S-EPMC3728334 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature