3A2C

Crystal structure of a pyrazolopyrimidine inhibitor complex bound to MAPKAP Kinase-2 (MK2)

3A2C の概要

• エントリーDOI: 10.2210/pdb3a2c/pdb
• 分子名称: MAP kinase-activated protein kinase 2, N~7~-(4-ethoxyphenyl)-6-methyl-N~5~-[(3S)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidine-5,7-diamine, SULFATE ION (3 entities in total)
• 機能のキーワード: gly-rich loop formed, aipha-helix, alternative splicing, atp-binding, kinase, nucleotide-binding, phosphoprotein, polymorphism, serine/threonine-protein kinase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 459147.09

構造登録者

Fujino, A.,Takimoto-Kamimura, M. (登録日: 2009-05-12, 公開日: 2010-05-12, 最終更新日: 2023-11-01)

主引用文献

Fujino, A.,Fukushima, K.,Namiki, N.,Kosugi, T.,Takimoto-Kamimura, M.
Structural analysis of an MK2-inhibitor complex: insight into the regulation of the secondary structure of the Gly-rich loop by TEI-I01800
Acta Crystallogr.,Sect.D, 66:80-87, 2010

PubMed Abstract: Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK2) is a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway and plays an important role in inflammatory diseases. The crystal structure of the complex of human MK2 (residues 41-364) with the potent MK2 inhibitor TEI-I01800 (pK(i) = 6.9) was determined at 2.9 A resolution. The MK2 structure in the MK2-TEI-I01800 complex is composed of two domains, as observed for other Ser/Thr kinases; however, the Gly-rich loop in the N-terminal domain forms an alpha-helix structure and not a beta-sheet. TEI-I01800 binds to the ATP-binding site as well as near the substrate-binding site of MK2. Both TEI-I01800 molecules have a nonplanar conformation that differs from those of other MK2 inhibitors deposited in the Protein Data Bank. The MK2-TEI-I01800 complex structure is the first active MK2 with an alpha-helical Gly-rich loop and TEI-I01800 regulates the secondary structure of the Gly-rich loop.

PubMed: 20057052
DOI: 10.1107/S0907444909046411

実験手法

X-RAY DIFFRACTION (2.9 Å)