View source for 7pje


==Inhibiting parasite proliferation using a rationally designed anti-tubulin agent==
<StructureSection load='7pje' size='340' side='right'caption='[[7pje]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pje]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Tetrahymena_thermophila Tetrahymena thermophila] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PJE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PJE 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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=7pje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pje OCA], [https://pdbe.org/7pje PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pje RCSB], [https://www.ebi.ac.uk/pdbsum/7pje PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pje ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TBA_TETTH TBA_TETTH] 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 ==
Infectious diseases caused by apicomplexan parasites remain a global public health threat. The presence of multiple ligand-binding sites in tubulin makes this protein an attractive target for anti-parasite drug discovery. However, despite remarkable successes as anti-cancer agents, the rational development of protozoan parasite-specific tubulin drugs has been hindered by a lack of structural and biochemical information on protozoan tubulins. Here, we present atomic structures for a protozoan tubulin and microtubule and delineate the architectures of apicomplexan tubulin drug-binding sites. Based on this information, we rationally designed the parasite-specific tubulin inhibitor parabulin and show that it inhibits growth of parasites while displaying no effects on human cells. Our work presents for the first time the rational design of a species-specific tubulin drug providing a framework to exploit structural differences between human and protozoa tubulin variants enabling the development of much-needed, novel parasite inhibitors.

Inhibiting parasite proliferation using a rationally designed anti-tubulin agent.,Gaillard N, Sharma A, Abbaali I, Liu T, Shilliday F, Cook AD, Ehrhard V, Bangera M, Roberts AJ, Moores CA, Morrissette N, Steinmetz MO EMBO Mol Med. 2021 Nov 8;13(11):e13818. doi: 10.15252/emmm.202013818. Epub 2021 , Oct 18. PMID:34661376<ref>PMID:34661376</ref>

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

==See Also==
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Tetrahymena thermophila]]
[[Category: Ehrhard VA]]
[[Category: Gaillard N]]
[[Category: Sharma A]]
[[Category: Steinmetz MO]]