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PDBsum entry 3fy2
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Human epha3 kinase and juxtamembrane region bound to substrate kqwdnyefiw
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Structure:
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Ephrin type-a receptor 3. Chain: a. Fragment: juxtamembrane segment and kinase domain: residues 577-947. Synonym: tyrosine-protein kinase receptor etk1, hek, hek4, tyrosine- protein kinase tyro4. Engineered: yes. Mutation: yes. Peptide substrate. Chain: b.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: epha3, etk, etk1, hek, tyro4. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide
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Resolution:
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1.80Å
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R-factor:
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0.181
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R-free:
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0.212
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Authors:
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T.Davis,J.R.Walker,F.Mackenzie,C.Bountra,J.Weigelt,C.H.Arrowsmith, A.M.Edwards,A.Bochkarev,S.Dhe-Paganon,Structural Genomics Consortium (Sgc)
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Key ref:
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T.L.Davis
et al.
(2009).
Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases.
Febs J,
276,
4395-4404.
PubMed id:
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Date:
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21-Jan-09
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Release date:
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03-Feb-09
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PROCHECK
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Headers
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References
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P16466
(HLYA_PROMI) -
Hemolysin from Proteus mirabilis
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Seq:
Struc:
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1577 a.a.
285 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 245 residue positions (black
crosses)
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Enzyme class:
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E.C.2.7.10.1
- receptor protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Febs J
276:4395-4404
(2009)
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PubMed id:
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Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases.
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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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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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Links
