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1t45
From Proteopedia
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[[Image:1t45.jpg|left|200px]] | [[Image:1t45.jpg|left|200px]] | ||
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'''STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE''' | '''STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE''' | ||
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[[Category: Wilson, K P.]] | [[Category: Wilson, K P.]] | ||
[[Category: Zou, H.]] | [[Category: Zou, H.]] | ||
| - | [[Category: | + | [[Category: Autoinhibition]] |
| - | [[Category: | + | [[Category: Kinase]] |
| - | [[Category: | + | [[Category: Structure]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:30:06 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 06:30, 3 May 2008
STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE
Overview
The activity of the c-Kit receptor protein-tyrosine kinase is tightly regulated in normal cells, whereas deregulated c-Kit kinase activity is implicated in the pathogenesis of human cancers. The c-Kit juxtamembrane region is known to have an autoinhibitory function; however the precise mechanism by which c-Kit is maintained in an autoinhibited state is not known. We report the 1.9-A resolution crystal structure of native c-Kit kinase in an autoinhibited conformation and compare it with active c-Kit kinase. Autoinhibited c-Kit is stabilized by the juxtamembrane domain, which inserts into the kinase-active site and disrupts formation of the activated structure. A 1.6-A crystal structure of c-Kit in complex with STI-571 (Imatinib or Gleevec) demonstrates that inhibitor binding disrupts this natural mechanism for maintaining c-Kit in an autoinhibited state. Together, these results provide a structural basis for understanding c-Kit kinase autoinhibition and will facilitate the structure-guided design of specific inhibitors that target the activated and autoinhibited conformations of c-Kit kinase.
About this Structure
1T45 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase., Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN, Snell GP, Zou H, Sang BC, Wilson KP, J Biol Chem. 2004 Jul 23;279(30):31655-63. Epub 2004 Apr 29. PMID:15123710 Page seeded by OCA on Sat May 3 09:30:06 2008
Categories: Homo sapiens | Single protein | Transferase | Dougan, D R. | Kraus, M L. | Mol, C D. | Sang, B C. | Scheibe, D N. | Schneider, T R. | Skene, R J. | Snell, G P. | Wilson, K P. | Zou, H. | Autoinhibition | Kinase | Structure
