Structural highlights
Publication Abstract from PubMed
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-alpha and other cytokines. In a previous report, it was shown that MK2 in complex with the selective inhibitor TEI-I01800 adopts an alpha-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 beta-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.
Structure of the beta-form of human MK2 in complex with the non-selective kinase inhibitor TEI-L03090.,Fujino A, Fukushima K, Kubota T, Matsumoto Y, Takimoto-Kamimura M Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Dec;69(Pt 12):1344-8. doi:, 10.1107/S1744309113030534. Epub 2013 Nov 28. PMID:24316826[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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 Struct Biol Cryst Commun. 2013 Dec;69(Pt 12):1344-8. doi:, 10.1107/S1744309113030534. Epub 2013 Nov 28. PMID:24316826 doi:http://dx.doi.org/10.1107/S1744309113030534
