2pzr
| |||||||
| , resolution 3.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | FGFR2, BEK, KSAM (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Strucure of FGF Receptor 2 (FGFR2) Kinase Domain Harboring the Pathogenic K641R Mutation Responsible for Pfeiffer Syndrome
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Antley-Bixler syndrome, 207410 ( OMIM:[176943], Apert syndrome OMIM:[176943], Beare-Stevenson cutis gyrata syndrome OMIM:[176943], Craniofacial-skeletal-dermatologic dysplasia OMIM:[176943], Craniosynostosis, nonspecific OMIM:[176943], Crouzon syndrome OMIM:[176943], Gastric cancer, somatic OMIM:[176943], Jackson-Weiss syndrome OMIM:[176943], Pfeiffer syndrome OMIM:[176943], Saethre-Chotzen syndrome OMIM:[176943]
About this StructureAbout this Structure
2PZR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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