7z7d

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Current revision (13:29, 1 February 2024) (edit) (undo)
 
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====
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==Tubulin-Todalam-Vinblastine-complex==
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<StructureSection load='7z7d' size='340' side='right'caption='[[7z7d]]' scene=''>
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<StructureSection load='7z7d' size='340' side='right'caption='[[7z7d]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7z7d]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Z7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z7D FirstGlance]. <br>
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</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=7z7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z7d OCA], [https://pdbe.org/7z7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z7d RCSB], [https://www.ebi.ac.uk/pdbsum/7z7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z7d ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4I2:N-(4-{2-[3-(trifluoromethyl)anilino]-1,3-thiazol-4-yl}phenyl)acetamide'>4I2</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VLB:(2ALPHA,2BETA,3BETA,4ALPHA,5BETA)-VINCALEUKOBLASTINE'>VLB</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7z7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z7d OCA], [https://pdbe.org/7z7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z7d RCSB], [https://www.ebi.ac.uk/pdbsum/7z7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z7d ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In this study, we capitalized on our previously performed crystallographic fragment screen and developed the antitubulin small molecule Todalam with only two rounds of straightforward chemical synthesis. Todalam binds to a novel tubulin site, disrupts microtubule networks in cells, arrests cells in G2/M, induces cell death, and synergizes with vinblastine. The compound destabilizes microtubules by acting as a molecular plug that sterically inhibits the curved-to-straight conformational switch in the alpha-tubulin subunit, and by sequestering tubulin dimers into assembly incompetent oligomers. Our results describe for the first time the generation of a fully rationally designed small molecule tubulin inhibitor from a fragment, which displays a unique molecular mechanism of action. They thus demonstrate the usefulness of tubulin-binding fragments as valuable starting points for innovative antitubulin drug and chemical probe discovery campaigns.
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Rational Design of a Novel Tubulin Inhibitor with a Unique Mechanism of Action.,Muhlethaler T, Milanos L, Ortega JA, Blum TB, Gioia D, Roy B, Prota AE, Cavalli A, Steinmetz MO Angew Chem Int Ed Engl. 2022 Jun 20;61(25):e202204052. doi: , 10.1002/anie.202204052. Epub 2022 Apr 25. PMID:35404502<ref>PMID:35404502</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7z7d" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
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*[[Tubulin 3D Structures|Tubulin 3D Structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bos taurus]]
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[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Rattus norvegicus]]
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[[Category: Blum TB]]
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[[Category: Cavalli A]]
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[[Category: Gioia D]]
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[[Category: Milanos L]]
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[[Category: Muehlethaler T]]
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[[Category: Ortega JA]]
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[[Category: Prota AE]]
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[[Category: Roy B]]
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[[Category: Steinmetz MO]]

Current revision

Tubulin-Todalam-Vinblastine-complex

PDB ID 7z7d

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