We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Tyrosine kinase inhibition: Ligand binding and conformational change in c-Kit and c-Abl
- Authors
Healy, Eamonn F.; Johnson, Skylar; Hauser, Charles R.; King, Peter J.
- Abstract
Abstract: The conformational flexibility exhibited by protein kinases poses an enormous challenge to the design of cancer therapeutics. Additionally the high degree of structural conservation within the kinase superfamily often leads to inhibitors that exhibit little selectivity and substantial cross reactivity. This work investigates the conformational changes that accompany the binding of Gleevec, or imatinib mesylate, to the tyrosine kinases c-Kit and c-Abl. Our analysis is that this fit is driven, at least in part, by the need to exclude water from solvent-exposed backbone hydrogen bonds. Both experimental and molecular modeling studies of the active state inhibitor of the tyrosine kinase c-Abl indicate that solvent exclusion also plays a role in this system.
- Subjects
PROTEIN-tyrosine kinases; MOLECULAR dynamics; LIGANDS (Biochemistry); PROTEIN binding; CANCER treatment; METHANESULFONATES; IMATINIB; CELL receptors
- Publication
FEBS Letters, 2009, Vol 583, Issue 17, p2899
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2009.07.051