title: 5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner.
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.
authors.affiliation: Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sogabe
authors.affiliation: Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima, Tokyo 196-8666, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Carna Biosciences, Inc., 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kirii
authors.affiliation: Carna Biosciences, Inc., 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sawa
authors.affiliation: Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. Electronic address: kinotk@b.s.osakafu-u.ac.jp.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry*; D048688:MAP Kinase Kinase 7 / Q000737:chemistry* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D015025:Zearalenone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000008:administration & dosage; D007783:Lactones; D012118:Resorcinols
chemical_list: D000255:Adenosine Triphosphate; D003545:Cysteine; D048688:MAP Kinase Kinase 7; D019950:Mitogen-Activated Protein Kinase 1; D015025:Zearalenone; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols
keywords: Covalent bonding inhibitor; Crystal structure; Cysteine; MAP kinase kinase 7