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New page: left|200px<br /> <applet load="2pwl" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pwl, resolution 2.4Å" /> '''Crystal Strucure of ...
 
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[[Image:2pwl.gif|left|200px]]<br />
[[Image:2pwl.jpg|left|200px]]<br /><applet load="2pwl" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="2pwl" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="2pwl, resolution 2.4&Aring;" />
caption="2pwl, resolution 2.4&Aring;" />
'''Crystal Strucure of FGF Receptor 2 (FGFR2) Kinase Domain Harboring the Pathogenic N549H Mutation Responsible for Crouzon Syndrome.'''<br />
'''Crystal Strucure of FGF Receptor 2 (FGFR2) Kinase Domain Harboring the Pathogenic N549H Mutation Responsible for Crouzon Syndrome.'''<br />
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==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==
2PWL 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 and ABG as [http://en.wikipedia.org/wiki/ligands ligands]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2PWL OCA].  
2PWL 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> and <scene name='pdbligand=ABG:'>ABG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=2PWL OCA].  


==Reference==
==Reference==
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[[Category: transferase]]
[[Category: transferase]]


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