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PDBsum entry 4o4l
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Cell cycle/inhibitor
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PDB id
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4o4l
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Contents |
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439 a.a.
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428 a.a.
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123 a.a.
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351 a.a.
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PDB id:
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| Name: |
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Cell cycle/inhibitor
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Title:
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Tubulin-peloruside a-epothilone a complex
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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. Fragment: unp residues 49-189.
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Source:
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Bos taurus. Bovine,cow,domestic cattle,domestic cow. Organism_taxid: 9913. Other_details: brain. Rattus norvegicus. Rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.20Å
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R-factor:
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0.188
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R-free:
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0.224
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Authors:
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A.E.Prota,K.Bargsten,P.T.Northcote,M.Marsh,K.H.Altmann,J.H.Miller, J.F.Diaz,M.O.Steinmetz
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Key ref:
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A.E.Prota
et al.
(2014).
Structural basis of microtubule stabilization by laulimalide and peloruside A.
Angew Chem Int Ed Engl,
53,
1621-1625.
PubMed id:
DOI:
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Date:
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18-Dec-13
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Release date:
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26-Mar-14
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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.
439 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.
428 a.a.
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DOI no:
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Angew Chem Int Ed Engl
53:1621-1625
(2014)
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PubMed id:
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Structural basis of microtubule stabilization by laulimalide and peloruside A.
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A.E.Prota,
K.Bargsten,
P.T.Northcote,
M.Marsh,
K.H.Altmann,
J.H.Miller,
J.F.Díaz,
M.O.Steinmetz.
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ABSTRACT
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Laulimalide and peloruside A are microtubule-stabilizing agents (MSAs), the
mechanism of action on microtubules of which is poorly defined. Here, using
X-ray crystallography it is shown that laulimalide and peloruside A bind to a
unique non-taxane site on β-tubulin and use their respective macrolide core
structures to interact with a second tubulin dimer across protofilaments. At the
same time, they allosterically stabilize the taxane-site M-loop that establishes
lateral tubulin contacts in microtubules. Structures of ternary complexes of
tubulin with laulimalide/peloruside A and epothilone A are also solved, and
a crosstalk between the laulimalide/peloruside and taxane sites via the M-loop
of β-tubulin is found. Together, the data define the mechanism of action of
laulimalide and peloruside A on tubulin and microtubules. The data further
provide a structural framework for understanding the synergy observed between
two classes of MSAs in tubulin assembly and the inhibition of cancer cell growth.
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