5JJ2
Crystal structure of the central domain of human AKAP18 gamma/delta in complex with malonate
Summary for 5JJ2
| Entry DOI | 10.2210/pdb5jj2/pdb |
| Descriptor | A-kinase anchor protein 7 isoform gamma, MALONATE ION (3 entities in total) |
| Functional Keywords | akap, a-kinase anchoring, phospoesterase, malonate, complex, central domain, hydrolase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Nucleus : Q9P0M2 |
| Total number of polymer chains | 1 |
| Total formula weight | 24826.46 |
| Authors | Bjerregaard-Andersen, K.,Ostensen, E.,Scott, J.D.,Tasken, K.,Morth, J.P. (deposition date: 2016-04-22, release date: 2016-08-03, Last modification date: 2024-01-10) |
| Primary citation | Bjerregaard-Andersen, K.,stensen, E.,Scott, J.D.,Tasken, K.,Morth, J.P. Malonate in the nucleotide-binding site traps human AKAP18 gamma / delta in a novel conformational state. Acta Crystallogr.,Sect.F, 72:591-597, 2016 Cited by PubMed Abstract: 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 AKAP18γ/δ 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, AKAP18γ/δ presents an interesting drug target with therapeutic potential in cardiovascular disease. The crystal structure of the central domain of human AKAP18γ has been determined at the atomic resolution of 1.25 Å. This first structure of human AKAP18γ 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 AKAP18γ 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 AKAP18γ at atomic resolution provides an excellent starting point for structure-guided drug design. PubMed: 27487922DOI: 10.1107/S2053230X16010189 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.25 Å) |
Structure validation
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