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| - | [[Image:2ogv.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2ogv| PDB=2ogv | SCENE= }} | | {{STRUCTURE_2ogv| PDB=2ogv | SCENE= }} |
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| - | '''Crystal Structure of the Autoinhibited Human c-Fms Kinase Domain'''
| + | ===Crystal Structure of the Autoinhibited Human c-Fms Kinase Domain=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17292918}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17292918 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17292918}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Macrophage colony stimulating factor receptor]] | | [[Category: Macrophage colony stimulating factor receptor]] |
| | [[Category: Receptor tyrosine kinase]] | | [[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 Tue Jul 29 03:37:06 2008'' |
Revision as of 00:37, 29 July 2008
Template:STRUCTURE 2ogv
Crystal Structure of the Autoinhibited Human c-Fms Kinase Domain
Template:ABSTRACT PUBMED 17292918
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
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