2psq
From Proteopedia
(New page: 200px<br /> <applet load="2psq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2psq, resolution 2.4Å" /> '''Crystal Structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2psq. | + | [[Image:2psq.jpg|left|200px]]<br /><applet load="2psq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2psq" size=" | + | |
caption="2psq, resolution 2.4Å" /> | caption="2psq, resolution 2.4Å" /> | ||
'''Crystal Structure of Unphosphorylated Unactivated Wild Type FGF Receptor 2 (FGFR2) Kinase Domain'''<br /> | '''Crystal Structure of Unphosphorylated Unactivated Wild Type FGF Receptor 2 (FGFR2) Kinase Domain'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
Activating mutations in the tyrosine kinase domain of receptor tyrosine, kinases (RTKs) cause cancer and skeletal disorders. Comparison of the, crystal structures of unphosphorylated and phosphorylated wild-type FGFR2, kinase domains with those of seven unphosphorylated pathogenic mutants, reveals an autoinhibitory "molecular brake" mediated by a triad of, residues in the kinase hinge region of all FGFRs. Structural analysis, shows that many other RTKs, including PDGFRs, VEGFRs, KIT, CSF1R, FLT3, TEK, and TIE, are also subject to regulation by this brake. Pathogenic, mutations activate FGFRs and other RTKs by disengaging the brake either, directly or indirectly. | Activating mutations in the tyrosine kinase domain of receptor tyrosine, kinases (RTKs) cause cancer and skeletal disorders. Comparison of the, crystal structures of unphosphorylated and phosphorylated wild-type FGFR2, kinase domains with those of seven unphosphorylated pathogenic mutants, reveals an autoinhibitory "molecular brake" mediated by a triad of, residues in the kinase hinge region of all FGFRs. Structural analysis, shows that many other RTKs, including PDGFRs, VEGFRs, KIT, CSF1R, FLT3, TEK, and TIE, are also subject to regulation by this brake. Pathogenic, mutations activate FGFRs and other RTKs by disengaging the brake either, directly or indirectly. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Antley-Bixler syndrome, 207410 ( OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Apert syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Beare-Stevenson cutis gyrata syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Craniofacial-skeletal-dermatologic dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Craniosynostosis, nonspecific OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Crouzon syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Gastric cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Jackson-Weiss syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Pfeiffer syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]], Saethre-Chotzen syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176943 176943]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2PSQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] Full crystallographic information is available from [http:// | + | 2PSQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PSQ OCA]. |
==Reference== | ==Reference== | ||
| Line 24: | Line 20: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:28:08 2008'' |
Revision as of 11:28, 23 January 2008
|
Crystal Structure of Unphosphorylated Unactivated Wild Type FGF Receptor 2 (FGFR2) Kinase Domain
Overview
Activating mutations in the tyrosine kinase domain of receptor tyrosine, kinases (RTKs) cause cancer and skeletal disorders. Comparison of the, crystal structures of unphosphorylated and phosphorylated wild-type FGFR2, kinase domains with those of seven unphosphorylated pathogenic mutants, reveals an autoinhibitory "molecular brake" mediated by a triad of, residues in the kinase hinge region of all FGFRs. Structural analysis, shows that many other RTKs, including PDGFRs, VEGFRs, KIT, CSF1R, FLT3, TEK, and TIE, are also subject to regulation by this brake. Pathogenic, mutations activate FGFRs and other RTKs by disengaging the brake either, directly or indirectly.
About this Structure
2PSQ is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Full crystallographic information is available from OCA.
Reference
A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases., Chen H, Ma J, Li W, Eliseenkova AV, Xu C, Neubert TA, Miller WT, Mohammadi M, Mol Cell. 2007 Sep 7;27(5):717-30. PMID:17803937
Page seeded by OCA on Wed Jan 23 13:28:08 2008
