3a2c
Crystal structure of a pyrazolopyrimidine inhibitor complex bound to MAPKAP Kinase-2 (MK2)Crystal structure of a pyrazolopyrimidine inhibitor complex bound to MAPKAP Kinase-2 (MK2)
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMitogen-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. Structural analysis of an MK2-inhibitor complex: insight into the regulation of the secondary structure of the Gly-rich loop by TEI-I01800.,Fujino A, Fukushima K, Namiki N, Kosugi T, Takimoto-Kamimura M Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):80-7. Epub 2009 Dec, 21. PMID:20057052[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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