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| [[Image:1t46.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1t46| PDB=1t46 | SCENE= }} | | {{STRUCTURE_1t46| PDB=1t46 | SCENE= }} |
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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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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_15123710}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15123710 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15123710}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Sti-571]] | | [[Category: Sti-571]] |
| [[Category: Structure]] | | [[Category: Structure]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:30:12 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:16:49 2008'' |
