Conformational equilibrium of N-myristoylated cAMP-dependent protein kinase A by molecular dynamics simulations.

ABSTRACT: The catalytic subunit of protein kinase A (PKA-C) is subject to several post- or cotranslational modifications that regulate its activity both spatially and temporally. Among those, N-myristoylation increases the kinase affinity for membranes and might also be implicated in substrate recognition and allosteric regulation. Here, we investigated the effects of N-myristoylation on the structure, dynamics, and conformational equilibrium of PKA-C using atomistic molecular dynamics simulations. We found that the myristoyl group inserts into the hydrophobic pocket and leads to a tighter packing of the A-helix against the core of the enzyme. As a result, the conformational dynamics of the A-helix are reduced and its motions are more coupled with the active site. Our simulations suggest that cation

SUBMITTER: Cembran A 

PROVIDER: S-EPMC3545707 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature