Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation.

ABSTRACT: Dramatic functional changes of enzyme usually require scores of alterations in amino acid sequence. However, in the case of guanylate kinase (GK), the functional novelty is induced by a single (S→P) mutation, leading to the functional transition of the enzyme from a phosphoryl transfer kinase into a phosphorprotein interaction domain. Here, by using molecular dynamic (MD) and metadynamics simulations, we provide a comprehensive description of the conformational transitions of the enzyme after mutating serine to proline. Our results suggest that the serine plays a crucial role in maintaining the closed conformation of wild-type GK and the GMP recognition. On the contrary, the S→P mutant exhibits a stable open conformation and loses the ability of ligand binding, which explains its functiona

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC4325336 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature