1z2b: Difference between revisions

Revision as of 18:38, 10 September 2015

Tubulin-colchicine-vinblastine: stathmin-like domain complex

Structural highlights

1z2b is a 5 chain structure with sequence from Bos taurus and Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	CN2, GDP, GTP, MG, VLB
Related:	1sa0, 1sa1
Gene:	Stmn4 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[STMN4_RAT] Exhibits microtubule-destabilizing activity.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Vinblastine is one of several tubulin-targeting Vinca alkaloids that have been responsible for many chemotherapeutic successes since their introduction in the clinic as antitumour drugs. In contrast with the two other classes of small tubulin-binding molecules (Taxol and colchicine), the binding site of vinblastine is largely unknown and the molecular mechanism of this drug has remained elusive. Here we report the X-ray structure of vinblastine bound to tubulin in a complex with the RB3 protein stathmin-like domain (RB3-SLD). Vinblastine introduces a wedge at the interface of two tubulin molecules and thus interferes with tubulin assembly. Together with electron microscopical and biochemical data, the structure explains vinblastine-induced tubulin self-association into spiral aggregates at the expense of microtubule growth. It also shows that vinblastine and the amino-terminal part of RB3-SLD binding sites share a hydrophobic groove on the alpha-tubulin surface that is located at an intermolecular contact in microtubules. This is an attractive target for drugs designed to perturb microtubule dynamics by interfacial interference, for which tubulin seems ideally suited because of its propensity to self-associate.

Structural basis for the regulation of tubulin by vinblastine.,Gigant B, Wang C, Ravelli RB, Roussi F, Steinmetz MO, Curmi PA, Sobel A, Knossow M Nature. 2005 May 26;435(7041):519-22. PMID:15917812^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nakao C, Itoh TJ, Hotani H, Mori N. Modulation of the stathmin-like microtubule destabilizing activity of RB3, a neuron-specific member of the SCG10 family, by its N-terminal domain. J Biol Chem. 2004 May 28;279(22):23014-21. Epub 2004 Mar 22. PMID:15039434 doi:https://dx.doi.org/10.1074/jbc.M313693200
↑ Gavet O, El Messari S, Ozon S, Sobel A. Regulation and subcellular localization of the microtubule-destabilizing stathmin family phosphoproteins in cortical neurons. J Neurosci Res. 2002 Jun 1;68(5):535-50. PMID:12111843 doi:https://dx.doi.org/10.1002/jnr.10234
↑ Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004 Mar 11;428(6979):198-202. PMID:15014504 doi:https://dx.doi.org/10.1038/nature02393
↑ Gigant B, Wang C, Ravelli RB, Roussi F, Steinmetz MO, Curmi PA, Sobel A, Knossow M. Structural basis for the regulation of tubulin by vinblastine. Nature. 2005 May 26;435(7041):519-22. PMID:15917812 doi:10.1038/nature03566

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OCA

[1] Nakao C, Itoh TJ, Hotani H, Mori N. Modulation of the stathmin-like microtubule destabilizing activity of RB3, a neuron-specific member of the SCG10 family, by its N-terminal domain. J Biol Chem. 2004 May 28;279(22):23014-21. Epub 2004 Mar 22. PMID:15039434 doi:https://dx.doi.org/10.1074/jbc.M313693200

[2] Gavet O, El Messari S, Ozon S, Sobel A. Regulation and subcellular localization of the microtubule-destabilizing stathmin family phosphoproteins in cortical neurons. J Neurosci Res. 2002 Jun 1;68(5):535-50. PMID:12111843 doi:https://dx.doi.org/10.1002/jnr.10234

[3] Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004 Mar 11;428(6979):198-202. PMID:15014504 doi:https://dx.doi.org/10.1038/nature02393

[4] Gigant B, Wang C, Ravelli RB, Roussi F, Steinmetz MO, Curmi PA, Sobel A, Knossow M. Structural basis for the regulation of tubulin by vinblastine. Nature. 2005 May 26;435(7041):519-22. PMID:15917812 doi:10.1038/nature03566

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[2]

[3]

[4]

@@ Line 2: / Line 2: @@
 <StructureSection load='1z2b' size='340' side='right' caption='[[1z2b]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1z2b]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z2B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z2B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1z2b]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z2B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z2B FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CN2:2-MERCAPTO-N-[1,2,3,10-TETRAMETHOXY-9-OXO-5,6,7,9-TETRAHYDRO-BENZO[A]HEPTALEN-7-YL]ACETAMIDE'>CN2</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VLB:(2ALPHA,2BETA,3BETA,4ALPHA,5BETA)-VINCALEUKOBLASTINE'>VLB</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sa0|1sa0]], [[1sa1|1sa1]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Stmn4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Stmn4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z2b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1z2b RCSB], [http://www.ebi.ac.uk/pdbsum/1z2b PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z2b OCA], [http://pdbe.org/1z2b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1z2b RCSB], [http://www.ebi.ac.uk/pdbsum/1z2b PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1z2b" style="background-color:#fffaf0;"></div>
 ==See Also==
+*[[Stathmin|Stathmin]]
 *[[Tubulin|Tubulin]]
 == References ==
@@ Line 36: / Line 38: @@
 </StructureSection>
 [[Category: Bos taurus]]
-[[Category: Rattus norvegicus]]
+[[Category: Buffalo rat]]
 [[Category: Curmi, P A]]
 [[Category: Gigant, B]]

1z2b: Difference between revisions

Revision as of 18:38, 10 September 2015

Tubulin-colchicine-vinblastine: stathmin-like domain complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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