Structural Bioinformatics-Based Design of Selective, Irreversible Kinase Inhibitors
摘要：
The active sites of 491 human protein kinase domains are highly conserved, which makes the design of selective inhibitors a formidable challenge. We used a structural bioinformatics approach to identify two selectivity filters, a threonine and a cysteine, at defined positions in the active site of p90 ribosornal protein S6 kinase (RSK). A fluoromethylketone inhibitor, designed to exploit both selectivity filters, potently and selectively inactivated RSK1 and RSK2 in mammalian cells. Kinases with only one selectivity filter were resistant to the inhibitor, yet they became sensitized after genetic introduction of the second selectivity filter. Thus, two amino acids that distinguish RSK from other protein kinases are sufficient to confer inhibitor sensitivity.
展开
DOI：
10.1126/science1108367
被引量：
年份：
2005
万方医学
掌桥科研
Semantic Scholar
Semantic Scholar
(全网免费下载)
dx.doi.org
查看更多
NCBI
NCBI
NCBI
(全网免费下载)
Pubmed Central
(全网免费下载)
Oxford Univ Press
JSTOR
Europe PMC
(全网免费下载)
Europe PMC
AIP
Cell Press
JBC
AACR
AGRIS
adsabs.harvard.edu
dialnet.unirioja.es
ProQuest
ResearchGate
EBSCO
EBSCO
Citeseer
(全网免费下载)
storage.ku.edu.tr
(全网免费下载)
biochemj.org
cmgm.stanford.edu
(全网免费下载)
sciencemag.org
biochem.stanford.edu
(全网免费下载)
highbeam.com
mcponline.org
mendeley.com
ohsu.pure.elsevier.com
fasebj.org
mmbr.asm.org
erc.endocrinology-journals.org
home.ku.edu.tr
(全网免费下载)
f1000.com
onAcademic
leaddiscovery.co.uk
scienceopen.com
cmgm3.stanford.edu
(全网免费下载)
emboj.embopress.org
ukpmc.ac.uk
portal.ku.edu.tr
(全网免费下载)
sciencemag.org
(全网免费下载)
biochemsoctrans.org
www.socolar.com
bbs.pku.edu.cn
(全网免费下载)
molpharm.aspetjournals.org
Semantic Scholar
(全网免费下载)
NCBI
(全网免费下载)
Europe PMC
(全网免费下载)
Pubmed Central
(全网免费下载)
Citeseer
(全网免费下载)
cmgm3.stanford.edu
(全网免费下载)
cmgm.stanford.edu
(全网免费下载)
storage.ku.edu.tr
(全网免费下载)
portal.ku.edu.tr
(全网免费下载)
biochem.stanford.edu
(全网免费下载)
bbs.pku.edu.cn
(全网免费下载)
home.ku.edu.tr
(全网免费下载)
sciencemag.org
(全网免费下载)
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
来源期刊
引用走势
站内活动
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
