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1z2b

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Tubulin-colchicine-vinblastine: stathmin-like domain complex

Structural highlights

1z2b is a 5 chain structure with sequence from Bos taurus and Rattus norvegicus. The July 2014 RCSB PDB Molecule of the Month feature on Microtubules by David Goodsell is 10.2210/rcsb_pdb/mom_2014_7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 4.1Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TBA1D_BOVIN Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).

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^[1]

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

References

↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1z2b"

@@ Line 3: / Line 3: @@
 <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/Buffalo_rat Buffalo rat]. The July 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Microtubules''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_7 10.2210/rcsb_pdb/mom_2014_7]. 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://proteopedia.org/fgij/fg.htm?mol=1Z2B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1z2b]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. The July 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Microtubules''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_7 10.2210/rcsb_pdb/mom_2014_7]. 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 [https://proteopedia.org/fgij/fg.htm?mol=1Z2B FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.1&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1sa0|1sa0]], [[1sa1|1sa1]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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'>[https://proteopedia.org/fgij/fg.htm?mol=1z2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z2b OCA], [https://pdbe.org/1z2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z2b RCSB], [https://www.ebi.ac.uk/pdbsum/1z2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z2b ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1z2b ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT]] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref>
+[https://www.uniprot.org/uniprot/TBA1D_BOVIN TBA1D_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 34: / Line 33: @@
 *[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
 *[[Tubulin 3D Structures|Tubulin 3D Structures]]
-*[[User:Alisa Cario|User:Alisa Cario]]
 == References ==
 <references/>
@@ Line 40: / Line 38: @@
 </StructureSection>
 [[Category: Bos taurus]]
-[[Category: Buffalo rat]]
 [[Category: Large Structures]]
 [[Category: Microtubules]]
 [[Category: RCSB PDB Molecule of the Month]]
-[[Category: Curmi, P A]]
+[[Category: Rattus norvegicus]]
-[[Category: Gigant, B]]
+[[Category: Curmi PA]]
-[[Category: Knossow, M]]
+[[Category: Gigant B]]
-[[Category: Ravelli, R B.G]]
+[[Category: Knossow M]]
-[[Category: Roussi, F]]
+[[Category: Ravelli RBG]]
-[[Category: Sobel, A]]
+[[Category: Roussi F]]
-[[Category: Steinmetz, M O]]
+[[Category: Sobel A]]
-[[Category: Wang, C]]
+[[Category: Steinmetz MO]]
-[[Category: Alpha-tubulin]]
+[[Category: Wang C]]
-[[Category: Beta-tubulin]]
-[[Category: Cell cycle]]
-[[Category: Colchicine]]
-[[Category: Gtpase]]
-[[Category: Microtubule]]
-[[Category: Stathmin]]
-[[Category: Tubulin]]
-[[Category: Vinblastine]]

1z2b

From Proteopedia

Current revision

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?)

Views

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