3FHR

High resolution crystal structure of mitogen-activated protein kinase-activated protein kinase 3 (MK3)-inhibitor complex

Summary for 3FHR

• Entry DOI: 10.2210/pdb3fhr/pdb
• Descriptor: MAP kinase-activated protein kinase 3, 2-(2-QUINOLIN-3-YLPYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE (3 entities in total)
• Functional Keywords: kinase-inhibitor complex, atp-binding, kinase, nucleotide-binding, nucleus, phosphoprotein, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q16644
• Total number of polymer chains: 1
• Total formula weight: 38915.36

Authors

Cheng, R.K.Y.,Barker, J.,Palan, S.,Felicetti, B.,Whittaker, M.,Hesterkamp, T. (deposition date: 2008-12-10, release date: 2009-12-15, Last modification date: 2024-03-20)

Primary citation

Cheng, R.,Felicetti, B.,Palan, S.,Toogood-Johnson, I.,Scheich, C.,Barker, J.,Whittaker, M.,Hesterkamp, T.
High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand
Protein Sci., 19:168-173, 2010

PubMed Abstract: The Mapkap kinases 2 and 3 (MK2 and MK3) have been implicated in intracellular signaling pathways leading to the production of the pro-inflammatory cytokine tumor necrosis factor alpha. MK2 has been pursued by the biopharmaceutical industry for many years for the development of a small molecule anti-inflammatory treatment and drug-like inhibitors have been described. The development of some of these compounds, however, has been slowed by the absence of a high-resolution crystal structure of MK2. Herein we present a high-resolution (1.9 A) crystal structure of the highly homologous MK3 in complex with a pharmaceutical lead compound. While all of the canonical features of Ser/Thr kinases in general and MK2 in particular are recapitulated in MK3, the detailed analysis of the binding interaction of the drug-like ligand within the adenine binding pocket allows relevant conclusions to be drawn for the further design of potent and selective drug candidates.

PubMed: 19937655
DOI: 10.1002/pro.294

Experimental method

X-RAY DIFFRACTION (1.9 Å)