3WZU

THE STRUCTURE OF MAP2K7 IN COMPLEX WITH 5Z-7-oxozeaenol

Summary for 3WZU

• Entry DOI: 10.2210/pdb3wzu/pdb
• Descriptor: Dual specificity mitogen-activated protein kinase kinase 7, (3S,5Z,8S,9S,11E)-8,9,16-trihydroxy-14-methoxy-3-methyl-3,4,9,10-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione (3 entities in total)
• Functional Keywords: protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O14733
• Total number of polymer chains: 1
• Total formula weight: 37361.28

Authors

Sogabe, Y.,Hashimoto, Y.,Matsumoto, T.,Kinoshita, T. (deposition date: 2014-10-07, release date: 2015-01-14, Last modification date: 2023-11-08)

Primary citation

Sogabe, Y.,Matsumoto, T.,Hashimoto, T.,Kirii, Y.,Sawa, M.,Kinoshita, T.
5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner.
Bioorg.Med.Chem.Lett., 25:593-596, 2015

PubMed Abstract: 5Z-7-Oxozeaenol (5Z7O) is a covalent bonding inhibitor against the several protein kinases (e.g., ERK2 and TAK1) that possess a free cysteine at the gatekeeper-2 position. In addition to this cysteine, MAP2K7 has three other cysteine residues that are candidate for covalent bonding by the inhibitor 5Z7O. The crystal structure of the MAP2K7/5Z7O complex revealed that the inhibitor binds to MAP2K7 at a cysteine residue located at the end of the hinge region and not at the gatekeeper-2 residue. The structural insights into the interaction of 5Z7O with MAP2K7 should aid the development of 5Z7O derivatives with improved potency and selectivity.

PubMed: 25529738
DOI: 10.1016/j.bmcl.2014.12.011

Experimental method

X-RAY DIFFRACTION (3.01 Å)