5syc

<StructureSection load='5syc' size='340' side='right'caption='[[5syc]], [[Resolution|resolution]] 3.50&Aring;' scene=''>

<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>

</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>

<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='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>

[[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.

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.

 

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== References ==

</StructureSection>

[[Category: Kellogg, E H]]

[[Category: Nogales, E]]

[[Category: Structural protein]]