Role of N-Terminal Myristylation in the Structure and Regulation of cAMP-Dependent Protein Kinase

摘要: The catalytic (C) subunit of cAMP-dependent protein kinase [protein A (PKA)] is a major target cAMP signaling, and its regulation fundamental importance to biological processes. One mode N-myristylation, which has eluded structural functional characterization so far because most crystal structures are the non-myristylated enzyme, phosphorylated on Ser10, generally lack electron density for first 13 residues. We crystallized myristylated wild-type (WT) PKA K7C mutant as binary (bound substrate peptide) ternary [bound peptide adenosine-5′-(β,γ-imido)triphosphate] complexes. There was clear entire N-terminus in complexes, both refined 2.0 A, complex, 1.35 A. N-termini these three display novel conformation with previously unseen helix from residues 1 7. appears have more stable N-terminus, this correlated significant decrease B-factors myr-K7C complexes compared WT complex. disordered previous structures. In addition ordered exhibited 53% increase kcat. effect nucleotide binding structure kinetic changes suggest that myristylation or occupancy myristyl pocket may serve site allosteric C-subunit.