5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner

作者：Sogabe Yuri; Matsumoto Takashi; Hashimoto Takuma; Kirii Yasuyuki; Sawa Masaaki; Kinoshita Takayoshi^*

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(3): 593-596.

DOI：10.1016/j.bmcl.2014.12.011

• MAP kinase kinase 7
• Covalent bonding inhibitor
• Cysteine
• Crystal structure

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.

• 出版日期2015-2-1