5syc: Difference between revisions

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==Near-atomic resolution cryo-EM reconstruction of peloruside-stabilized microtubule==
==Near-atomic resolution cryo-EM reconstruction of peloruside-stabilized microtubule==
<StructureSection load='5syc' size='340' side='right' caption='[[5syc]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
<SX load='5syc' size='340' side='right' viewer='molstar' caption='[[5syc]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5syc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYC FirstGlance]. <br>
<table><tr><td colspan='2'>[[5syc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SYC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=POU:PELORUSIDE+A'>POU</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5sye|5sye]], [[5syf|5syf]], [[5syg|5syg]]</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POU:PELORUSIDE+A'>POU</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5syc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syc OCA], [http://pdbe.org/5syc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5syc RCSB], [http://www.ebi.ac.uk/pdbsum/5syc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5syc ProSAT]</span></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=5syc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syc OCA], [https://pdbe.org/5syc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5syc RCSB], [https://www.ebi.ac.uk/pdbsum/5syc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5syc ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/B6A7R0_PIG B6A7R0_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.[RuleBase:RU000352][SAAS:SAAS00540896] [[http://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.
[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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A number of microtubule (MT)-stabilizing agents (MSAs) have demonstrated or predicted potential as anticancer agents, but a detailed structural basis for their mechanism of action is still lacking. We have obtained high-resolution (3.9-4.2A) cryo-electron microscopy (cryo-EM) reconstructions of MTs stabilized by the taxane-site binders Taxol and zampanolide, and by peloruside, which targets a distinct, non-taxoid pocket on beta-tubulin. We find that each molecule has unique distinct structural effects on the MT lattice structure. Peloruside acts primarily at lateral contacts and has an effect on the "seam" of heterologous interactions, enforcing a conformation more similar to that of homologous (i.e., non-seam) contacts by which it regularizes the MT lattice. In contrast, binding of either Taxol or zampanolide induces MT heterogeneity. In doubly bound MTs, peloruside overrides the heterogeneity induced by Taxol binding. Our structural analysis illustrates distinct mechanisms of these drugs for stabilizing the MT lattice and is of relevance to the possible use of combinations of MSAs to regulate MT activity and improve therapeutic potential.


Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures.,Kellogg EH, Hejab NM, Howes S, Northcote P, Miller JH, Diaz JF, Downing KH, Nogales E J Mol Biol. 2017 Jan 17. pii: S0022-2836(17)30015-3. doi:, 10.1016/j.jmb.2017.01.001. PMID:28104363<ref>PMID:28104363</ref>
==See Also==
 
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5syc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</SX>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
[[Category: Kellogg, E H]]
[[Category: Kellogg EH]]
[[Category: Nogales, E]]
[[Category: Nogales E]]
[[Category: Microtubule]]
[[Category: Peloruside]]
[[Category: Structural protein]]

Latest revision as of 17:18, 6 March 2024

Near-atomic resolution cryo-EM reconstruction of peloruside-stabilized microtubuleNear-atomic resolution cryo-EM reconstruction of peloruside-stabilized microtubule

5syc, resolution 3.50Å

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