This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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
