Binding site multiplicity with fatty acid ligands: implications for the regulation of PKR kinase autophosphorylation with palmitate.

ABSTRACT: Saturated long chain-free fatty acids (FFAs), especially palmitate, have been implicated in apoptosis by inhibiting the activity of PKR (double-stranded RNA-dependent protein kinase). We recently found evidence that palmitate interacts directly with the kinase domain of PKR, subsequently inhibiting the autophosphorylation of PKR. To investigate the interactions of palmitate with PKR and its effects on PKR autophosphorylation, we performed extensive unbiased MD simulations combined with biochemical and biophysical experiments. The simulations predict multiple putative binding sites of palmitate on both the phosphorylated and unphosphorylated PKR with similar binding affinities. Ligand-protein interactions involving a large variety of different binding modes challenge the conventional view o

SUBMITTER: Fang L 

PROVIDER: S-EPMC4177322 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature