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PDBsum entry 3fy2
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References listed in PDB file
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Key reference
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Title
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Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases.
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Authors
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T.L.Davis,
J.R.Walker,
A.Allali-Hassani,
S.A.Parker,
B.E.Turk,
S.Dhe-Paganon.
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Ref.
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Febs J, 2009,
276,
4395-4404.
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PubMed id
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Abstract
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Ephrin receptor tyrosine kinase A3 (EphA3, EC 2.7.10.1) is a member of a unique
branch of the kinome in which downstream signaling occurs in both ligand- and
receptor-expressing cells. Consequently, the ephrins and ephrin receptor
tyrosine kinases often mediate processes involving cell-cell contact, including
cellular adhesion or repulsion, developmental remodeling and neuronal mapping.
The receptor is also frequently overexpressed in invasive cancers, including
breast, small-cell lung and gastrointestinal cancers. However, little is known
about direct substrates of EphA3 kinase and no chemical probes are available.
Using a library approach, we found a short peptide sequence that is a good
substrate for EphA3 and is suitable for co-crystallization studies. Complex
structures show multiple contacts between kinase and substrates; in particular,
two residues undergo conformational changes and by mutation are found to be
important for substrate binding and turnover. In addition, a difference in
catalytic efficiency between EPH kinase family members is observed. These
results provide insight into the mechanism of substrate binding to these
developmentally integral enzymes.
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