کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2048403 | 1074079 | 2009 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Tyrosine kinase inhibition: Ligand binding and conformational change in c-Kit and c-Abl Tyrosine kinase inhibition: Ligand binding and conformational change in c-Kit and c-Abl](/preview/png/2048403.png)
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.
Journal: FEBS Letters - Volume 583, Issue 17, 3 September 2009, Pages 2899–2906