5jj2

Publication Abstract from PubMed

A-kinase anchoring proteins (AKAPs) are a family of proteins that provide spatiotemporal resolution of protein kinase A (PKA) phosphorylation. In the myocardium, PKA and AKAP18gamma/delta are found in complex with sarcoendoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and phospholamban (PLB). This macromolecular complex provides a means by which anchored PKA can dynamically regulate cytoplasmic Ca(2+) release and re-uptake. For this reason, AKAP18gamma/delta presents an interesting drug target with therapeutic potential in cardiovascular disease. The crystal structure of the central domain of human AKAP18gamma has been determined at the atomic resolution of 1.25 A. This first structure of human AKAP18gamma is trapped in a novel conformation by a malonate molecule bridging the important R-loop with the 2H phosphoesterase motif. Although the physiological substrate of AKAP18gamma is currently unknown, a potential proton wire deep in the central binding crevice has been indentified, leading to bulk solvent below the R-loop. Malonate complexed with AKAP18gamma at atomic resolution provides an excellent starting point for structure-guided drug design.

Malonate in the nucleotide-binding site traps human AKAP18gamma/delta in a novel conformational state.,Bjerregaard-Andersen K, Ostensen E, Scott JD, Tasken K, Morth JP Acta Crystallogr F Struct Biol Commun. 2016 Aug;72(Pt 8):591-7. doi:, 10.1107/S2053230X16010189. Epub 2016 Jul 13. PMID:27487922^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.