1z2b

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:03, 23 August 2023) (edit) (undo)
 
(13 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1z2b.gif|left|200px]]
 
-
{{Structure
+
==Tubulin-colchicine-vinblastine: stathmin-like domain complex==
-
|PDB= 1z2b |SIZE=350|CAPTION= <scene name='initialview01'>1z2b</scene>, resolution 4.10&Aring;
+
<StructureSection load='1z2b' size='340' side='right'caption='[[1z2b]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <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&#39;-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5&#39;-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VLB:(2ALPHA,2&#39;BETA,3BETA,4ALPHA,5BETA)-VINCALEUKOBLASTINE'>VLB</scene>
+
<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>
-
|ACTIVITY=
+
</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>
-
|GENE= Stmn4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
+
<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>
-
|DOMAIN=
+
<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>
-
|RELATEDENTRY=[[1sa0|1SA0]], [[1sa1|1SA1]]
+
</table>
-
|RESOURCES=<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.ebi.ac.uk/pdbsum/1z2b PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1z2b RCSB]</span>
+
== Function ==
-
}}
+
[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]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z2/1z2b_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1z2b ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== 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.
-
'''Tubulin-colchicine-vinblastine: stathmin-like domain complex'''
+
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<ref>PMID:15917812</ref>
 +
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>
-
==Overview==
+
==See Also==
-
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.
+
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
-
 
+
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
-
==About this Structure==
+
== References ==
-
1Z2B is a [[Protein complex]] structure of sequences 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].
+
<references/>
-
 
+
__TOC__
-
==Reference==
+
</StructureSection>
-
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:[http://www.ncbi.nlm.nih.gov/pubmed/15917812 15917812]
+
[[Category: Bos taurus]]
[[Category: Bos taurus]]
-
[[Category: Protein complex]]
+
[[Category: Large Structures]]
 +
[[Category: Microtubules]]
 +
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
-
[[Category: Curmi, P A.]]
+
[[Category: Curmi PA]]
-
[[Category: Gigant, B.]]
+
[[Category: Gigant B]]
-
[[Category: Knossow, M.]]
+
[[Category: Knossow M]]
-
[[Category: Ravelli, R B.G.]]
+
[[Category: Ravelli RBG]]
-
[[Category: Roussi, F.]]
+
[[Category: Roussi F]]
-
[[Category: Sobel, A.]]
+
[[Category: Sobel A]]
-
[[Category: Steinmetz, M O.]]
+
[[Category: Steinmetz MO]]
-
[[Category: Wang, C.]]
+
[[Category: Wang C]]
-
[[Category: alpha-tubulin]]
+
-
[[Category: beta-tubulin]]
+
-
[[Category: colchicine]]
+
-
[[Category: gtpase]]
+
-
[[Category: microtubule]]
+
-
[[Category: stathmin]]
+
-
[[Category: tubulin]]
+
-
[[Category: vinblastine]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:28:01 2008''
+

Current revision

Tubulin-colchicine-vinblastine: stathmin-like domain complex

PDB ID 1z2b

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

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