1t45
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span> |
|GENE= kit ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= kit ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1pkg|1PKG]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t45 OCA], [http://www.ebi.ac.uk/pdbsum/1t45 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t45 RCSB]</span> | ||
}} | }} | ||
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[[Category: Wilson, K P.]] | [[Category: Wilson, K P.]] | ||
[[Category: Zou, H.]] | [[Category: Zou, H.]] | ||
| - | [[Category: autoinhibition]] | + | [[Category: autoinhibition,]] |
[[Category: kinase]] | [[Category: kinase]] | ||
[[Category: structure]] | [[Category: structure]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:50:59 2008'' |
Revision as of 20:51, 30 March 2008
| |||||||
| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | kit (Homo sapiens) | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Related: | 1PKG
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Sun Mar 30 23:50:59 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
