1TVO
The structure of ERK2 in complex with a small molecule inhibitor
Summary for 1TVO
| Entry DOI | 10.2210/pdb1tvo/pdb |
| Descriptor | Mitogen-activated protein kinase 1, 5-(2-PHENYLPYRAZOLO[1,5-A]PYRIDIN-3-YL)-1H-PYRAZOLO[3,4-C]PYRIDAZIN-3-AMINE (3 entities in total) |
| Functional Keywords | kinase, protein-inhibitor complex, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton, spindle : P28482 |
| Total number of polymer chains | 1 |
| Total formula weight | 42558.78 |
| Authors | Kinoshita, T. (deposition date: 2004-06-30, release date: 2005-09-13, Last modification date: 2024-03-13) |
| Primary citation | Ohori, M.,Kinoshita, T.,Okubo, M.,Sato, K.,Yamazaki, A.,Arakawa, H.,Nishimura, S.,Inamura, N.,Nakajima, H.,Neya, M.,Miyake, H.,Fujii, T. Identification of a selective ERK inhibitor and structural determination of the inhibitor-ERK2 complex Biochem.Biophys.Res.Commun., 336:357-363, 2005 Cited by PubMed Abstract: Selective inhibition of extracellular signal-regulated kinase (ERK) represents a potential approach for the treatment of cancer and other diseases; however, no selective inhibitors are currently available. Here, we describe an ERK-selective inhibitor, FR180204, and determine the structural basis of its selectivity. FR180204 inhibited the kinase activity of ERK1 and ERK2, with K(i) values 0.31 and 0.14microM, respectively. Lineweaver-Burk analysis of the binding interaction revealed that FR180204 acted as competitive inhibitor of ATP. In mink lung epithelial Mv1Lu cells, FR180204 inhibited TGFbeta-induced luciferase-expression. X-ray crystal structure analysis of the human ERK2/FR180204 complex revealed that Q105, D106, L156, and C166, which form the ATP-binding pocket on ERK, play important roles in the drug/protein interaction. These results suggest that FR180204 is an ERK-selective and cell-permeable inhibitor, and could be useful for elucidating the roles of ERK as well as for drug development. PubMed: 16139248DOI: 10.1016/j.bbrc.2005.08.082 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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