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PDBsum entry 4ybk
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PDB id:
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Transferase
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Title:
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C-helix-out dasatinib analog crystallized with c-src kinase
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Structure:
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Proto-oncogene tyrosine-protein kinase src. Chain: a. Fragment: unp residues 251-533. Synonym: proto-oncogenE C-src,pp60c-src,p60-src. Engineered: yes
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Source:
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Gallus gallus. Chicken. Organism_taxid: 9031. Gene: src. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.50Å
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R-factor:
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0.208
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R-free:
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0.252
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Authors:
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F.E.Kwarcinski,K.B.Brandvold,T.K.Johnson,S.Phadke,J.L.Meagher, M.A.Seeliger,J.A.Stuckey,M.B.Soellner
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Key ref:
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F.E.Kwarcinski
et al.
(2016).
Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.
Acs Chem Biol,
11,
1296-1304.
PubMed id:
DOI:
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Date:
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18-Feb-15
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Release date:
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02-Mar-16
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PROCHECK
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Headers
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References
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P00523
(SRC_CHICK) -
Proto-oncogene tyrosine-protein kinase Src from Gallus gallus
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Seq:
Struc:
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533 a.a.
266 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.10.2
- non-specific 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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DOI no:
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Acs Chem Biol
11:1296-1304
(2016)
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PubMed id:
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Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.
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F.E.Kwarcinski,
K.R.Brandvold,
S.Phadke,
O.M.Beleh,
T.K.Johnson,
J.L.Meagher,
M.A.Seeliger,
J.A.Stuckey,
M.B.Soellner.
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ABSTRACT
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In the kinase field, there are many widely held tenets about
conformation-selective inhibitors that have yet to be validated using controlled
experiments. We have designed, synthesized, and characterized a series of kinase
inhibitor analogues of dasatinib, an FDA-approved kinase inhibitor that binds
the active conformation. This inhibitor series includes two Type II inhibitors
that bind the DFG-out inactive conformation and two inhibitors that bind the
αC-helix-out inactive conformation. Using this series of compounds, we analyze
the impact that conformation-selective inhibitors have on target binding and
kinome-wide selectivity.
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Links
