A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket
| Autor: | Sheri Rogers, Charles L. Cywin, Liang Tong, Susan Pav, Della White, Kathy Crane, Christopher Pargellis, Maryanne L. Brown |
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| Rok vydání: | 1997 |
| Předmět: |
Models
Molecular Pyridines Serine threonine protein kinase Mitogen-activated protein kinase kinase Crystallography X-Ray p38 Mitogen-Activated Protein Kinases Biochemistry MAP2K7 Adenosine Triphosphate Structural Biology Genetics Humans Computer Simulation c-Raf Enzyme Inhibitors Protein kinase A Binding Sites biology Cyclin-dependent kinase 2 Imidazoles Recombinant Proteins Calcium-Calmodulin-Dependent Protein Kinases Cyclin-dependent kinase complex biology.protein Mitogen-Activated Protein Kinases Casein kinase 2 |
| Zdroj: | Nature Structural Biology. 4:311-316 |
| ISSN: | 1072-8368 |
| Popis: | The crystal structure of human p38 mitogen-activated protein (MAP) kinase in complex with a potent and highly specific pyridinyl-imidazole inhibitor has been determined at 2.0 A resolution. The structure of the kinase, which is in its unphosphorylated state, is similar to that of the closely-related ERK2. The inhibitor molecule is bound in the ATP pocket. A hydrogen bond is made between the pyridyl nitrogen of the inhibitor and the main chain amido nitrogen of residue 109, analogous to the interaction from the N1 atom of ATP. The crystal structure provides possible explanations for the specificity of this class of inhibitors. Other protein kinase inhibitors may achieve their specificity through a similar mechanism. The structure also reveals a possible second binding site for this inhibitor, with currently unknown function. |
| Databáze: | OpenAIRE |
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