5sb5: Difference between revisions
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==Tubulin-todalam-9-complex== | |||
<StructureSection load='5sb5' size='340' side='right'caption='[[5sb5]], [[Resolution|resolution]] 2.31Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5sb5]] 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=5SB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SB5 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4CJ:N-{4-[2-(3-fluoroanilino)-1,3-thiazol-4-yl]phenyl}acetamide'>4CJ</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></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=5sb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sb5 OCA], [https://pdbe.org/5sb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sb5 RCSB], [https://www.ebi.ac.uk/pdbsum/5sb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sb5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5sb5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]] | |||
*[[Tubulin 3D Structures|Tubulin 3D Structures]] | |||
*[[Tubulin tyrosine ligase 3D structures|Tubulin tyrosine ligase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Gallus gallus]] | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Blum TB]] | |||
[[Category: Cavalli A]] | |||
[[Category: Gioia D]] | |||
[[Category: Milanos L]] | |||
[[Category: Muehlethaler T]] | |||
[[Category: Ortega JA]] | |||
[[Category: Prota AE]] | |||
[[Category: Steinmetz MO]] | |||