Changes in protein kinase A conformational entropy by ATP-competitive inhibitors

NMR characterization of the structural and dynamic changes of the catalytic subunit of cAMP-dependent protein kinase A (PKA-C) in complex with balanol and H89, two ATP-competitive inhibitors. This study aims to unveil how these two inhibitors affect the PKA-C structure and dynamics and how these changes govern the enzyme binding cooperativity and conformational dynamic. These data are part of a paper that has been sent to a peer-review paper.

Description
Proton and Nitrogen chemical shift files from NMR TROSY-HSQC spectra of PKA-C bound to balanol and H89, with or w/t pseudo-substrate peptide (PKI). These list files have been used for chemical shift perturbation (CSP) plots, CHEmical Shift Covariance Analysis (CHESCA), and COordiNate ChemIcal Shift bEhavior (CONCISE) analysis. Correlation scores vs. residue derived from CHESCA analysis for the balanol/ and H89/PKA-C complexes and their correlation with the binding cooperativity coefficient of the enzyme bound to different nucleotide/inhibitors. Calculation of the conformational energy derived from the fast-dynamics of the methyl group side chains of Isoleucine, Leucine, and Valin (ILV) residues of PKA-C bound to nucleotide/inhibitors.

Funding information
Sponsorship: NIH GM100310 and S10 OD021536 to Gianluigi Veglia

Referenced by
ATP-Competitive Inhibitors Modulate the Substrate Binding Cooperativity of a Kinase by Altering its Conformational Entropy