View source for 7nb8


==Plasmodium falciparum kinesin-5 motor domain without nucleotide, complexed with 14 protofilament microtubule.==
<StructureSection load='7nb8' size='340' side='right'caption='[[7nb8]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nb8]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NB8 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]] 4.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G2P:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANYLATE+ESTER'>G2P</scene>, <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=7nb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nb8 OCA], [https://pdbe.org/7nb8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nb8 RCSB], [https://www.ebi.ac.uk/pdbsum/7nb8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nb8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TBA1B_PIG TBA1B_PIG] 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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== Publication Abstract from PubMed ==
Plasmodium parasites cause malaria and are responsible annually for hundreds of thousands of deaths. Kinesins are a superfamily of microtubule-dependent ATPases that play important roles in the parasite replicative machinery, which is a potential target for antiparasite drugs. Kinesin-5, a molecular motor that cross-links microtubules, is an established antimitotic target in other disease contexts, but its mechanism in Plasmodium falciparum is unclear. Here, we characterized P. falciparum kinesin-5 (PfK5) using cryo-EM to determine the motor's nucleotide-dependent microtubule-bound structure and introduced 3D classification of individual motors into our microtubule image processing pipeline to maximize our structural insights. Despite sequence divergence in PfK5, the motor exhibits classical kinesin mechanochemistry, including ATP-induced subdomain rearrangement and cover neck bundle formation, consistent with its plus-ended directed motility. We also observed that an insertion in loop5 of the PfK5 motor domain creates a different environment in the well-characterized human kinesin-5 drug-binding site. Our data reveal the possibility for selective inhibition of PfK5 and can be used to inform future exploration of Plasmodium kinesins as antiparasite targets.

Cryo-EM structure of a microtubule-bound parasite kinesin motor and implications for its mechanism and inhibition.,Cook AD, Roberts AJ, Atherton J, Tewari R, Topf M, Moores CA J Biol Chem. 2021 Nov;297(5):101063. doi: 10.1016/j.jbc.2021.101063. Epub 2021 , Aug 8. PMID:34375637<ref>PMID:34375637</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Kinesin 3D Structures|Kinesin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Sus scrofa]]
[[Category: Atherton J]]
[[Category: Cook AD]]
[[Category: Moores CA]]
[[Category: Roberts A]]
[[Category: Tewari R]]
[[Category: Topf M]]