| Autor: |
Furet, Pascal, Caravatti, Giorgio, Lydon, Nicholas, Priestle, John P., Sowadski, Janusz M., Trinks, Uwe, Traxler, Peter |
| Zdroj: |
Journal of Computer-Aided Molecular Design; December 1995, Vol. 9 Issue: 6 p465-472, 8p |
| Abstrakt: |
A model for the binding mode of the potent protein kinase inhibitor staurosporine is proposed. Using the information provided by the crystal structure of the cyclic-AMP-dependent protein kinase, it is suggested that staurosporine, despite a seemingly unrelated chemical structure, exploits the same key hydrogen-bond interactions as ATP, the cofactor of the protein kinases, in its binding mode. The structure-activity relationships of the inhibitor and a docking analysis give strong support to this protein tyrosine kinase is rationalized on the basis of the model. It is proposed that this selectivity originates in the occupancy, by one of the anilino moieties of the inhibitor, of the region of the enzyme cleft that normally binds the ribose ring of ATP, which appears to possess a marked lipophilic character in this kinase. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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