View source for 6qtn


==Tubulin-cyclostreptin complex==
<StructureSection load='6qtn' size='340' side='right'caption='[[6qtn]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qtn]] 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=6QTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QTN 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=JHH:Cyclostreptin'>JHH</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=6qtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qtn OCA], [https://pdbe.org/6qtn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qtn RCSB], [https://www.ebi.ac.uk/pdbsum/6qtn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qtn 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 ==
It has been proposed that one of the mechanisms of taxane-site ligand-mediated tubulin activation is modulation of the structure of a switch element (the M-loop) from a disordered form in dimeric tubulin to a folded helical structure in microtubules. Here, we used covalent taxane-site ligands, including cyclostreptin, to gain further insight into this mechanism. The crystal structure of cyclostreptin-bound tubulin reveals covalent binding to betaHis229, but no stabilization of the M-loop. The capacity of cyclostreptin to induce microtubule assembly compared to other covalent taxane-site agents demonstrates that the induction of tubulin assembly is not strictly dependent on M-loop stabilization. We further demonstrate that most covalent taxane-site ligands are able to partially overcome drug resistance mediated by betaIII-tubulin (betaIII) overexpression in HeLa cells, and compare their activities to pironetin, an interfacial covalent inhibitor of tubulin assembly that displays invariant growth inhibition in these cells. Our findings suggest a relationship between a diminished interaction of taxane-site ligands with betaIII-tubulin and betaIII tubulin-mediated drug resistance. This supports the idea that overexpression of betaIII increases microtubule dynamicity by counteracting the enhanced microtubule stability promoted by covalent taxane-site binding ligands.

Crystal Structure of the Cyclostreptin-Tubulin Adduct: Implications for Tubulin Activation by Taxane-Site Ligands.,Balaguer FA, Muhlethaler T, Estevez-Gallego J, Calvo E, Gimenez-Abian JF, Risinger AL, Sorensen EJ, Vanderwal CD, Altmann KH, Mooberry SL, Steinmetz MO, Oliva MA, Prota AE, Diaz JF Int J Mol Sci. 2019 Mar 20;20(6). pii: ijms20061392. doi: 10.3390/ijms20061392. PMID:30897704<ref>PMID:30897704</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qtn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Altmann K-H]]
[[Category: Balaguer FdA]]
[[Category: Calvo E]]
[[Category: Diaz JF]]
[[Category: Estevez-Gallego J]]
[[Category: Gimenez-Abian JF]]
[[Category: Mooberry SL]]
[[Category: Muehlethaler T]]
[[Category: Oliva MA]]
[[Category: Prota AE]]
[[Category: Risinger AL]]
[[Category: Sorensen EJ]]
[[Category: Steinmetz MO]]
[[Category: Vanderwal CD]]