4o4l

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{{STRUCTURE_4o4l| PDB=4o4l | SCENE= }}
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==Tubulin-Peloruside A-Epothilone A complex==
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===Tubulin-Peloruside A-Epothilone A complex===
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<StructureSection load='4o4l' size='340' side='right' caption='[[4o4l]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24470331}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4o4l]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O4L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O4L FirstGlance]. <br>
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==Function==
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EP:EPOTHILONE+A'>EP</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POU:PELORUSIDE+A'>POU</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4o4h|4o4h]], [[4o4i|4o4i]], [[4o4j|4o4j]]</td></tr>
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<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=4o4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o4l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o4l RCSB], [http://www.ebi.ac.uk/pdbsum/4o4l PDBsum]</span></td></tr>
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</table>
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== Function ==
[[http://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN]] 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. [[http://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT]] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref> [[http://www.uniprot.org/uniprot/TBB2B_BOVIN TBB2B_BOVIN]] 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 (By similarity).
[[http://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN]] 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. [[http://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT]] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref> [[http://www.uniprot.org/uniprot/TBB2B_BOVIN TBB2B_BOVIN]] 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 (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Laulimalide and peloruside A are microtubule-stabilizing agents (MSAs), the mechanism of action on microtubules of which is poorly defined. Here, using X-ray crystallography it is shown that laulimalide and peloruside A bind to a unique non-taxane site on beta-tubulin and use their respective macrolide core structures to interact with a second tubulin dimer across protofilaments. At the same time, they allosterically stabilize the taxane-site M-loop that establishes lateral tubulin contacts in microtubules. Structures of ternary complexes of tubulin with laulimalide/peloruside A and epothilone A are also solved, and a crosstalk between the laulimalide/peloruside and taxane sites via the M-loop of beta-tubulin is found. Together, the data define the mechanism of action of laulimalide and peloruside A on tubulin and microtubules. The data further provide a structural framework for understanding the synergy observed between two classes of MSAs in tubulin assembly and the inhibition of cancer cell growth.
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Structural basis of microtubule stabilization by laulimalide and peloruside a.,Prota AE, Bargsten K, Northcote PT, Marsh M, Altmann KH, Miller JH, Diaz JF, Steinmetz MO Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1621-5. doi: 10.1002/anie.201307749., Epub 2014 Jan 27. PMID:24470331<ref>PMID:24470331</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4o4l]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O4L OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:024470331</ref><references group="xtra"/><references/>
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*[[Tubulin|Tubulin]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Altmann, K H.]]
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[[Category: Buffalo rat]]
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[[Category: Bargsten, K.]]
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[[Category: Chick]]
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[[Category: Diaz, J F.]]
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[[Category: Altmann, K H]]
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[[Category: Marsh, M.]]
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[[Category: Bargsten, K]]
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[[Category: Miller, J H.]]
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[[Category: Diaz, J F]]
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[[Category: Northcote, P T.]]
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[[Category: Marsh, M]]
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[[Category: Prota, A E.]]
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[[Category: Miller, J H]]
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[[Category: Steinmetz, M O.]]
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[[Category: Northcote, P T]]
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[[Category: Prota, A E]]
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[[Category: Steinmetz, M O]]
[[Category: Alpha-tubulin]]
[[Category: Alpha-tubulin]]
[[Category: Beta-tubulin]]
[[Category: Beta-tubulin]]

Revision as of 02:50, 25 December 2014

Tubulin-Peloruside A-Epothilone A complex

4o4l, resolution 2.20Å

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