title: Crystal structure of human ERK2 complexed with a pyrazolo[3,4-c]pyridazine derivative.
abstract: A series of pyrazolopyridazine compounds were briefly investigated as ERK2 inhibitors. The crystal structure of ERK2 complexed with an allyl derivative was determined. The compound induces structural change including movement of the glycine-rich loop and peptide flip between Met108-Glu109. As a result, the newly formed subsite can recognize small hydrophobic substituents but not hydrophilic ones.
authors.affiliation: Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. kinotk@b.s.osakafu-u.ac.jp
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Masaichi
authors.initials: M
authors.lastname: Warizaya
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohori
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Neya
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001667:Binding, Competitive; D018360:Crystallography, X-Ray / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006801:Humans; D008715:Methionine / Q000737:chemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D011720:Pyrazoles; D011725:Pyridines; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D008715:Methionine; D019950:Mitogen-Activated Protein Kinase 1; D005998:Glycine