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PDBsum entry 5njh
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Structural protein
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PDB id
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5njh
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Contents |
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435 a.a.
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413 a.a.
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121 a.a.
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339 a.a.
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References listed in PDB file
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Key reference
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Title
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Triazolopyrimidines are microtubule-Stabilizing agents that bind the vinca inhibitor site of tubulin.
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Authors
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G.Sáez-Calvo,
A.Sharma,
F.A.Balaguer,
I.Barasoain,
J.Rodríguez-Salarichs,
N.Olieric,
H.Muñoz-Hernández,
M...Berbís,
S.Wendeborn,
M.A.Peñalva,
R.Matesanz,
..Canales,
A.E.Prota,
J.Jímenez-Barbero,
J.M.Andreu,
C.Lamberth,
M.O.Steinmetz,
J.F.Díaz.
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Ref.
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Cell Chem Biol, 2017,
24,
737.
[DOI no: ]
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PubMed id
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Abstract
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Microtubule-targeting agents (MTAs) are some of the clinically most successful
anti-cancer drugs. Unfortunately, instances of multidrug resistances to MTA have
been reported, which highlights the need for developing MTAs with different
mechanistic properties. One less explored class of MTAs are
[1,2,4]triazolo[1,5-a]pyrimidines (TPs). These cytotoxic compounds are
microtubule-stabilizing agents that inexplicably bind to vinblastine binding
site on tubulin, which is typically targeted by microtubule-destabilizing
agents. Here we used cellular, biochemical, and structural biology approaches
to address this apparent discrepancy. Our results establish TPs as vinca-site
microtubule-stabilizing agents that promote longitudinal tubulin contacts in
microtubules, in contrast to classical microtubule-stabilizing agents that
primarily promote lateral contacts. Additionally we observe that TPs studied
here are not affected by p-glycoprotein overexpression, and suggest that TPs are
promising ligands against multidrug-resistant cancer cells.
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