2ogv
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2ogv.gif|left|200px]] | [[Image:2ogv.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2ogv", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_2ogv| PDB=2ogv | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal Structure of the Autoinhibited Human c-Fms Kinase Domain''' | '''Crystal Structure of the Autoinhibited Human c-Fms Kinase Domain''' | ||
| Line 35: | Line 32: | ||
[[Category: Wilks, A F.]] | [[Category: Wilks, A F.]] | ||
[[Category: Williams, N K.]] | [[Category: Williams, N K.]] | ||
| - | [[Category: | + | [[Category: Macrophage colony stimulating factor receptor]] |
| - | [[Category: | + | [[Category: Receptor tyrosine kinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:53:22 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:53, 4 May 2008
Crystal Structure of the Autoinhibited Human c-Fms Kinase Domain
Overview
c-Fms, a member of the Platelet-derived Growth Factor (PDGF) receptor family of receptor tyrosine kinases (RTKs), is the receptor for macrophage colony stimulating factor (CSF-1) that regulates proliferation, differentiation and survival of cells of the mononuclear phagocyte lineage. Abnormal expression of c-fms proto-oncogene is associated with a significant number of human pathologies, including a variety of cancers and rheumatoid arthritis. Accordingly, c-Fms represents an attractive therapeutic target. To further understand the regulation of c-Fms, we determined the 2.7 A resolution crystal structure of the cytosolic domain of c-Fms that comprised the kinase domain and the juxtamembrane domain. The structure reveals the crucial inhibitory role of the juxtamembrane domain (JM) that binds to a hydrophobic site immediately adjacent to the ATP binding pocket. This interaction prevents the activation loop from adopting an active conformation thereby locking the c-Fms kinase into an autoinhibited state. As observed for other members of the PDGF receptor family, namely c-Kit and Flt3, three JM-derived tyrosine residues primarily drive the mechanism for autoinhibition in c-Fms, therefore defining a common autoinhibitory mechanism within this family. Moreover the structure provides an understanding of c-Fms inhibition by Gleevec as well as providing a platform for the development of more selective inhibitors that target the inactive conformation of c-Fms kinase.
About this Structure
2OGV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The 2.7 A crystal structure of the autoinhibited human c-Fms kinase domain., Walter M, Lucet IS, Patel O, Broughton SE, Bamert R, Williams NK, Fantino E, Wilks AF, Rossjohn J, J Mol Biol. 2007 Mar 30;367(3):839-47. Epub 2007 Jan 20. PMID:17292918 Page seeded by OCA on Sun May 4 10:53:22 2008
