3EQB

X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP

Summary for 3EQB

• Entry DOI: 10.2210/pdb3eqb/pdb
• Related: 1S9I 1S9J 2P55
• Descriptor: Dual specificity mitogen-activated protein kinase kinase 1, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: protein kinase structure, mitogen activated protein kinase kinase, signal transduction, ligand co-complex, ternary co-complex with kinase, ligand and mgatp, non-competitive protein kinase inhibitor, transferase, acetylation, atp-binding, disease mutation, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, tyrosine-protein kinase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 37866.16

Authors

Ohren, J.F.,Pavlovsky, A.,Zhang, E. (deposition date: 2008-09-30, release date: 2008-11-11, Last modification date: 2023-09-06)

Primary citation

Warmus, J.S.,Flamme, C.,Zhang, L.Y.,Barrett, S.,Bridges, A.,Chen, H.,Gowan, R.,Kaufman, M.,Sebolt-Leopold, J.,Leopold, W.,Merriman, R.,Ohren, J.,Pavlovsky, A.,Przybranowski, S.,Tecle, H.,Valik, H.,Whitehead, C.,Zhang, E.
2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase).
Bioorg.Med.Chem.Lett., 18:6171-6174, 2008

PubMed Abstract: This paper reports a second generation MEK inhibitor. The previously reported potent and efficacious MEK inhibitor, PD-184352 (CI-1040), contains an integral hydroxamate moiety. This compound suffered from less than ideal solubility and metabolic stability. An oxadiazole moiety behaves as a bioisostere for the hydroxamate group, leading to a more metabolically stable and efficacious MEK inhibitor.

PubMed: 18951019
DOI: 10.1016/j.bmcl.2008.10.015

Experimental method

X-RAY DIFFRACTION (2.62 Å)