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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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PDB id:
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| Name: |
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Structural protein
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Title:
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Triazolopyrimidines stabilize microtubules by binding to the vinca inhibitor site of tubulin
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Structure:
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Tubulin alpha-1b chain. Chain: a, c. Synonym: alpha-tubulin ubiquitous,tubulin k-alpha-1,tubulin alpha- ubiquitous chain. Tubulin beta-2b chain. Chain: b, d. Stathmin-4. Chain: e. Synonym: stathmin-like protein b3,rb3.
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Source:
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Bos taurus. Bovine. Organism_taxid: 9913. Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: stmn4. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.39Å
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R-factor:
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0.218
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R-free:
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0.237
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Authors:
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A.Sharma,G.S.Calvo,A.E.Prota,J.F.Diaz,M.O.Steinmetz
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Key ref:
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G.Sáez-Calvo
et al.
(2017).
Triazolopyrimidines Are Microtubule-Stabilizing Agents that Bind the Vinca Inhibitor Site of Tubulin.
Cell Chem Biol,
24,
737.
PubMed id:
DOI:
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Date:
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28-Mar-17
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Release date:
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21-Jun-17
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PROCHECK
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Headers
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References
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P81947
(TBA1B_BOVIN) -
Tubulin alpha-1B chain from Bos taurus
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Seq:
Struc:
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451 a.a.
435 a.a.
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Q6B856
(TBB2B_BOVIN) -
Tubulin beta-2B chain from Bos taurus
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Seq:
Struc:
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445 a.a.
413 a.a.
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DOI no:
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Cell Chem Biol
24:737
(2017)
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PubMed id:
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Triazolopyrimidines Are Microtubule-Stabilizing Agents that Bind the Vinca Inhibitor Site of Tubulin.
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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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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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