View source for 7lxb


==HeLa-tubulin in complex with cryptophycin 52==
<StructureSection load='7lxb' size='340' side='right'caption='[[7lxb]], [[Resolution|resolution]] 3.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lxb]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LXB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.26&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=YGY:Cryptophycin+52'>YGY</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=7lxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lxb OCA], [https://pdbe.org/7lxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lxb RCSB], [https://www.ebi.ac.uk/pdbsum/7lxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lxb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TBA1B_HUMAN TBA1B_HUMAN] 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 ==
Cryptophycin-52 (Cp-52) is potentially the most potent anticancer drug known, with IC(50) values in the low picomolar range, but its binding site on tubulin and mechanism of action are unknown. Here, we have determined the binding site of Cp-52, and its parent compound, cryptophycin-1, on HeLa tubulin, to a resolution of 3.3 A and 3.4 A, respectively, by cryo-EM and characterized this binding further by molecular dynamics simulations. The binding site was determined to be located at the tubulin interdimer interface and partially overlap that of maytansine, another cytotoxic tubulin inhibitor. Binding induces curvature both within and between tubulin dimers that is incompatible with the microtubule lattice. Conformational changes occur in both alpha-tubulin and beta-tubulin, particularly in helices H8 and H10, with distinct differences between alpha and beta monomers and between Cp-52-bound and cryptophycin-1-bound tubulin. From these results, we have determined: (i) the mechanism of action of inhibition of both microtubule polymerization and depolymerization, (ii) how the affinity of Cp-52 for tubulin may be enhanced, and (iii) where linkers for targeted delivery can be optimally attached to this molecule.

,  PMID:34461087<ref>PMID:34461087</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lxb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Eren E]]