3WI6

Crystal structure of MAPKAP Kinase-2 (MK2) in complex with non-selective inhibitor

Summary for 3WI6

• Entry DOI: 10.2210/pdb3wi6/pdb
• Related: 3a2c
• Descriptor: MAP kinase-activated protein kinase 2, N-[(3S)-piperidin-3-yl]-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-5-amine (2 entities in total)
• Functional Keywords: gly-rich loop formed, atp-binding, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P49137
• Total number of polymer chains: 6
• Total formula weight: 226677.92

Authors

Fujino, A.,Fukushima, K.,Kubota, T.,Matsumoto, Y.,Takimoto-Kamimura, M. (deposition date: 2013-09-06, release date: 2013-12-18, Last modification date: 2023-11-08)

Primary citation

Fujino, A.,Fukushima, K.,Kubota, T.,Matsumoto, Y.,Takimoto-Kamimura, M.
Structure of the beta-form of human MK2 in complex with the non-selective kinase inhibitor TEI-L03090
Acta Crystallogr.,Sect.F, 69:1344-1348, 2013

PubMed Abstract: Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2), a serine/threonine kinase from the p38 mitogen-activated protein kinase signalling pathway, plays an important role in the production of TNF-α and other cytokines. In a previous report, it was shown that MK2 in complex with the selective inhibitor TEI-I01800 adopts an α-helical glycine-rich loop that is induced by the stable nonplanar conformer of TEI-I01800. To understand the mechanism of the structural change, the structure of MK2 bound to TEI-L03090, which lacks the key substituent found in TEI-I01800, was determined. MK2-TEI-L03090 has a β-sheet glycine-rich loop in common with other kinases, as predicted. This result suggests that a small compound can induce a drastic conformational change in the target protein structure and can be used to design potent and selective inhibitors.

PubMed: 24316826
DOI: 10.1107/S1744309113030534

Experimental method

X-RAY DIFFRACTION (2.99 Å)