View source for 5ocu


==Molecular basis of human kinesin-8 function and inhibition==
<SX load='5ocu' size='340' side='right' viewer='molstar' caption='[[5ocu]], [[Resolution|resolution]] 5.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ocu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=5OCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OCU 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]] 5.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TA1:TAXOL'>TA1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5ocu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ocu OCA], [https://pdbe.org/5ocu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ocu RCSB], [https://www.ebi.ac.uk/pdbsum/5ocu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ocu ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/TBB_PIG TBB_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 ==
Kinesin motors play diverse roles in mitosis and are targets for antimitotic drugs. The clinical significance of these motors emphasizes the importance of understanding the molecular basis of their function. Equally important, investigations into the modes of inhibition of these motors provide crucial information about their molecular mechanisms. Kif18A regulates spindle microtubules through its dual functionality, with microtubule-based stepping and regulation of microtubule dynamics. We investigated the mechanism of Kif18A and its inhibition by the small molecule BTB-1. The Kif18A motor domain drives ATP-dependent plus-end microtubule gliding, and undergoes conformational changes consistent with canonical mechanisms of plus-end-directed motility. The Kif18A motor domain also depolymerizes microtubule plus and minus ends. BTB-1 inhibits both of these microtubule-based Kif18A activities. A reconstruction of BTB-1-bound, microtubule-bound Kif18A, in combination with computational modeling, identified an allosteric BTB-1-binding site near loop5, where it blocks the ATP-dependent conformational changes that we characterized. Strikingly, BTB-1 binding is close to that of well-characterized Kif11 inhibitors that block tight microtubule binding, whereas BTB-1 traps Kif18A on the microtubule. Our work highlights a general mechanism of kinesin inhibition in which small-molecule binding near loop5 prevents a range of conformational changes, blocking motor function.

Structural basis of human kinesin-8 function and inhibition.,Locke J, Joseph AP, Pena A, Mockel MM, Mayer TU, Topf M, Moores CA Proc Natl Acad Sci U S A. 2017 Oct 23. pii: 201712169. doi:, 10.1073/pnas.1712169114. PMID:29078367<ref>PMID:29078367</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5ocu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Kinesin 3D Structures|Kinesin 3D Structures]]
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
== References ==
<references/>
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</SX>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Joseph AP]]
[[Category: Locke J]]
[[Category: Moores CA]]
[[Category: Topf M]]