3KC3

MK2 complexed to inhibitor N4-(7-(benzofuran-2-yl)-1H-indazol-5-yl)pyrimidine-2,4-diamine

Summary for 3KC3

• Entry DOI: 10.2210/pdb3kc3/pdb
• Related: 3KA0
• Descriptor: MAP kinase-activated protein kinase 2, N~4~-[7-(1-benzofuran-2-yl)-1H-indazol-5-yl]pyrimidine-2,4-diamine (3 entities in total)
• Functional Keywords: mapkap-k2, mk2, tnfalpha, diaminopyrimidine, atp-binding, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 12
• Total formula weight: 454021.88

Authors

Argiriadi, M.A.,Talanian, R.V.,Borhani, D.W. (deposition date: 2009-10-20, release date: 2010-01-12, Last modification date: 2024-02-21)

Primary citation

Argiriadi, M.A.,Ericsson, A.M.,Harris, C.M.,Banach, D.L.,Borhani, D.W.,Calderwood, D.J.,Demers, M.D.,Dimauro, J.,Dixon, R.W.,Hardman, J.,Kwak, S.,Li, B.,Mankovich, J.A.,Marcotte, D.,Mullen, K.D.,Ni, B.,Pietras, M.,Sadhukhan, R.,Sousa, S.,Tomlinson, M.J.,Wang, L.,Xiang, T.,Talanian, R.V.
2,4-Diaminopyrimidine MK2 inhibitors. Part I: Observation of an unexpected inhibitor binding mode.
Bioorg.Med.Chem.Lett., 20:330-333, 2010

PubMed Abstract: MK2 is a Ser/Thr kinase of significant interest as an anti-inflammatory drug discovery target. Here we describe the development of in vitro tools for the identification and characterization of MK2 inhibitors, including validation of inhibitor interactions with the crystallography construct and determination of the unique binding mode of 2,4-diaminopyrimidine inhibitors in the MK2 active site. Use of these tools in the optimization of a potent and selective inhibitor lead series is described in the accompanying Letter.

PubMed: 19919896
DOI: 10.1016/j.bmcl.2009.10.102

Experimental method

X-RAY DIFFRACTION (2.9 Å)