6M7H

Structure of calmodulin with KN93

6M7H の概要

• エントリーDOI: 10.2210/pdb6m7h/pdb
• 分子名称: Calmodulin-1, N-[2-[[[3-(4'-Chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4'-methoxybenzenesulfonamide, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: ca2+ binding ef-hand inhibitor complex, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18630.76

構造登録者

Damo, S.M.,Pattanayek, R.,Johnson, C.N. (登録日: 2018-08-20, 公開日: 2019-08-28, 最終更新日: 2024-10-16)

主引用文献

Johnson, C.N.,Pattanayek, R.,Potet, F.,Rebbeck, R.T.,Blackwell, D.J.,Nikolaienko, R.,Sequeira, V.,Le Meur, R.,Radwanski, P.B.,Davis, J.P.,Zima, A.V.,Cornea, R.L.,Damo, S.M.,Gyorke, S.,George Jr., A.L.,Knollmann, B.C.
The CaMKII inhibitor KN93-calmodulin interaction and implications for calmodulin tuning of NaV1.5 and RyR2 function.
Cell Calcium, 82:102063-102063, 2019

PubMed Abstract: Here we report the structure of the widely utilized calmodulin (CaM)-dependent protein kinase II (CaMKII) inhibitor KN93 bound to the Ca-sensing protein CaM. KN93 is widely believed to inhibit CaMKII by binding to the kinase. The CaM-KN93 interaction is significant as it can interfere with the interaction between CaM and it's physiological targets, thereby raising the possibility of ascribing modified protein function to CaMKII phosphorylation while concealing a CaM-protein interaction. NMR spectroscopy, stopped-flow kinetic measurements, and x-ray crystallography were used to characterize the structure and biophysical properties of the CaM-KN93 interaction. We then investigated the functional properties of the cardiac Na channel (Na1.5) and ryanodine receptor (RyR2). We find that KN93 disrupts a high affinity CaM-Na1.5 interaction and alters channel function independent of CaMKII. Moreover, KN93 increases RyR2 Ca release in cardiomyocytes independent of CaMKII. Therefore, when interpreting KN93 data, targets other than CaMKII need to be considered.

PubMed: 31401388
DOI: 10.1016/j.ceca.2019.102063

実験手法

X-RAY DIFFRACTION (1.6 Å)