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427 a.a.
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420 a.a.
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124 a.a.
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* Residue conservation analysis
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PDB id:
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Cell cycle
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Title:
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Tubulin: rb3 stathmin-like domain complex
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Structure:
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Tubulin alpha chain. Chain: a, c. Tubulin beta chain. Chain: b, d. Stathmin-4. Chain: e. Fragment: rb3 stathmin-like domain. Synonym: stathmin-like protein b3, rb3. Engineered: yes
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Source:
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Ovis aries. Sheep. Organism_taxid: 9940. Organ: brain. Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: stmn4. Expressed in: escherichia coli bl21(de3).
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Resolution:
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3.65Å
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R-factor:
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0.216
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R-free:
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0.254
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Authors:
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A.Dorleans,B.Gigant,R.B.G.Ravelli,P.Mailliet,V.Mikol,M.Knoss
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Key ref:
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A.Dorléans
et al.
(2009).
Variations in the colchicine-binding domain provide insight into the structural switch of tubulin.
Proc Natl Acad Sci U S A,
106,
13775-13779.
PubMed id:
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Date:
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23-May-09
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Release date:
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01-Sep-09
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PROCHECK
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Headers
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References
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D0VWZ0
(D0VWZ0_SHEEP) -
Tubulin alpha chain
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Seq:
Struc:
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451 a.a.
427 a.a.
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Gene Ontology (GO) functional annotation
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Cellular component
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protein complex
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4 terms
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Biological process
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intracellular signal transduction
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5 terms
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Biochemical function
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structural molecule activity
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4 terms
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Proc Natl Acad Sci U S A
106:13775-13779
(2009)
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PubMed id:
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Variations in the colchicine-binding domain provide insight into the structural switch of tubulin.
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A.Dorléans,
B.Gigant,
R.B.Ravelli,
P.Mailliet,
V.Mikol,
M.Knossow.
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ABSTRACT
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Structural changes occur in the alphabeta-tubulin heterodimer during the
microtubule assembly/disassembly cycle. Their most prominent feature is a
transition from a straight, microtubular structure to a curved structure. There
is a broad range of small molecule compounds that disturbs the microtubule
cycle, a class of which targets the colchicine-binding site and prevents
microtubule assembly. This class includes compounds with very different chemical
structures, and it is presently unknown whether they prevent tubulin
polymerization by the same mechanism. To address this issue, we have determined
the structures of tubulin complexed with a set of such ligands and show that
they interfere with several of the movements of tubulin subunits structural
elements upon its transition from curved to straight. We also determined the
structure of tubulin unliganded at the colchicine site; this reveals that a
beta-tubulin loop (termed T7) flips into this site. As with colchicine site
ligands, this prevents a helix which is at the interface with alpha-tubulin from
stacking onto a beta-tubulin beta sheet as in straight protofilaments. Whereas
in the presence of these ligands the interference with microtubule assembly gets
frozen, by flipping in and out the beta-subunit T7 loop participates in a
reversible way in the resistance to straightening that opposes microtubule
assembly. Our results suggest that it thereby contributes to microtubule dynamic
instability.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.J.Edwards,
J.A.Hadfield,
T.W.Wallace,
and
S.Ducki
(2011).
Tubulin-binding dibenz[c,e]oxepines as colchinol analogues for targeting tumour vasculature.
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Org Biomol Chem, 9,
219-231.
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N.M.O'Boyle,
L.M.Greene,
O.Bergin,
J.B.Fichet,
T.McCabe,
D.G.Lloyd,
D.M.Zisterer,
and
M.J.Meegan
(2011).
Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones.
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Bioorg Med Chem, 19,
2306-2325.
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R.A.Stanton,
K.M.Gernert,
J.H.Nettles,
and
R.Aneja
(2011).
Drugs that target dynamic microtubules: a new molecular perspective.
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Med Res Rev, 31,
443-481.
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R.Alvarez,
V.López,
C.Mateo,
M.Medarde,
and
R.Peláez
(2011).
New para-para Stilbenophanes: Synthesis by McMurry Coupling, Conformational Analysis and Inhibition of Tubulin Polymerisation.
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Chemistry, 17,
3406-3419.
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F.J.Fourniol,
C.V.Sindelar,
B.Amigues,
D.K.Clare,
G.Thomas,
M.Perderiset,
F.Francis,
A.Houdusse,
and
C.A.Moores
(2010).
Template-free 13-protofilament microtubule-MAP assembly visualized at 8 A resolution.
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J Cell Biol, 191,
463-470.
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PDB code:
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N.Nicolaus,
J.Zapke,
P.Riesterer,
J.M.Neudörfl,
A.Prokop,
H.Oschkinat,
and
H.G.Schmalz
(2010).
Azides derived from colchicine and their use in library synthesis: A practical entry to new bioactive derivatives of an old natural drug.
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ChemMedChem, 5,
661-665.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
