2JBO

Protein kinase MK2 in complex with an inhibitor (crystal form-1, soaking)

2JBO の概要

• エントリーDOI: 10.2210/pdb2jbo/pdb
• 関連するPDBエントリー: 1KWP 1NXK 1NY3 2JBP
• 分子名称: MAP KINASE-ACTIVATED PROTEIN KINASE 2, PHOSPHATE ION, 2-(2-QUINOLIN-3-YLPYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE, ... (4 entities in total)
• 機能のキーワード: ser-thr kinase, mapkap kinase 2, phosphorylation, mk2, kinase, atp site, transferase, atp-binding, serine/threonine-protein kinase, small molecule inhibitor, nucleotide-binding
• 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: 38100.81

構造登録者

Hillig, R.C.,Eberspaecher, U.,Monteclaro, F.,Huber, M.,Nguyen, D.,Mengel, A.,Muller-Tiemann, B.,Egner, U. (登録日: 2006-12-09, 公開日: 2007-03-20, 最終更新日: 2023-12-13)

主引用文献

Hillig, R.C.,Eberspaecher, U.,Monteclaro, F.,Huber, M.,Nguyen, D.,Mengel, A.,Muller-Tiemann, B.,Egner, U.
Structural Basis for a High Affinity Inhibitor Bound to Protein Kinase Mk2.
J.Mol.Biol., 369:735-, 2007

PubMed Abstract: The Ser/Thr protein kinase MAPKAP kinase 2 (MK2) plays a crucial role in inflammation. We determined the structure of the kinase domain of MK2 in complex with a low molecular mass inhibitor in two different crystal forms, obtained from soaking and co-crystallization. To our knowledge, these are the first structures of MK2 showing the binding mode of an inhibitor with high binding affinity (IC50 8.5 nM). The two crystal forms revealed conformational flexibility in the binding site and extend the experimental basis for rational drug design. Crystal form-1 contained one MK2 molecule per asymmetric unit. Form-2 contained 12 molecules, which arrange into two different types of MK2 trimers. One of them may serve as a model for an intermediate state during substrate phosphorylation, as each MK2 monomer places its activation segment into the substrate peptide binding groove of the trimer neighbor.

PubMed: 17449059
DOI: 10.1016/J.JMB.2007.03.004

実験手法

X-RAY DIFFRACTION (3.1 Å)