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PDBsum entry 4at4
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PDB id:
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Transferase
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Title:
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Crystal structure of trkb kinase domain in complex with ex429
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Structure:
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Bdnf/nt-3 growth factors receptor. Chain: a. Fragment: kinase domain, residues 543-838. Synonym: gp145-trkb, trk-b, neurotrophic tyrosine kinase receptor type 2, trkb tyrosine kinase, tropomyosin-related kinase b. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.
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Resolution:
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2.36Å
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R-factor:
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0.183
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R-free:
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0.217
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Authors:
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T.Bertrand,M.Kothe,J.Liu,A.Dupuy,A.Rak,P.F.Berne,S.Davis, T.Gladysheva,C.Valtre,J.Y.Crenne,M.Mathieu
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Key ref:
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T.Bertrand
et al.
(2012).
The crystal structures of TrkA and TrkB suggest key regions for achieving selective inhibition.
J Mol Biol,
423,
439-453.
PubMed id:
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Date:
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03-May-12
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Release date:
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22-Aug-12
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PROCHECK
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Headers
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References
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Q16620
(NTRK2_HUMAN) -
BDNF/NT-3 growth factors receptor from Homo sapiens
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Seq:
Struc:
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822 a.a.
292 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 3 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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J Mol Biol
423:439-453
(2012)
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PubMed id:
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The crystal structures of TrkA and TrkB suggest key regions for achieving selective inhibition.
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T.Bertrand,
M.Kothe,
J.Liu,
A.Dupuy,
A.Rak,
P.F.Berne,
S.Davis,
T.Gladysheva,
C.Valtre,
J.Y.Crenne,
M.Mathieu.
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ABSTRACT
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The Trk family of neurotrophin receptors, which includes the three highly
homologous proteins TrkA, TrkB and TrkC, is strongly associated with central and
peripheral nervous system processes. Trk proteins are also of interest in
oncology, since Trk activation has been observed in several cancer types. While
Trk kinases are attractive oncology targets, selectivity might be more of an
issue than for other kinases due to potential CNS side effects if several Trk
kinases are simultaneously targeted. In order to address this issue, we present
here the first structures of human TrkA and TrkB kinase domains and three
complexes between TrkB and Trk inhibitors. These structures reveal different
conformations of the kinase domain and suggest new regions of selectivity among
the Trk family.
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