5fnv: Difference between revisions
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==a new complex structure of tubulin with an alpha-beta unsaturated lactone== | ==a new complex structure of tubulin with an alpha-beta unsaturated lactone== | ||
<StructureSection load='5fnv' size='340' side='right' caption='[[5fnv]], [[Resolution|resolution]] 2.61Å' scene=''> | <StructureSection load='5fnv' size='340' side='right'caption='[[5fnv]], [[Resolution|resolution]] 2.61Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fnv]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FNV OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5fnv]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat], [http://en.wikipedia.org/wiki/Chick Chick] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FNV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FNV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=X3H:PIRONETIN'>X3H</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=X3H:PIRONETIN'>X3H</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5fnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fnv OCA], [http://pdbe.org/5fnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fnv RCSB], [http://www.ebi.ac.uk/pdbsum/5fnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fnv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5fnv" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5fnv" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]] | |||
*[[Tubulin 3D Structures|Tubulin 3D Structures]] | |||
*[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]] | |||
*[[User:Alisa Cario|User:Alisa Cario]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Buffalo rat]] | |||
[[Category: Chick]] | |||
[[Category: Large Structures]] | |||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Naismith, J]] | [[Category: Naismith, J]] | ||
Revision as of 10:27, 6 May 2020
a new complex structure of tubulin with an alpha-beta unsaturated lactonea new complex structure of tubulin with an alpha-beta unsaturated lactone
Structural highlights
Function[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. [STMN4_RAT] Exhibits microtubule-destabilizing activity.[1] [2] [3] [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. Publication Abstract from PubMedMolecules that alter the normal dynamics of microtubule assembly and disassembly include many anticancer drugs in clinical use. So far all such therapeutics target beta-tubulin, and structural biology has explained the basis of their action and permitted design of new drugs. However, by shifting the profile of beta-tubulin isoforms, cancer cells become resistant to treatment. Compounds that bind to alpha-tubulin are less well characterized and unexploited. The natural product pironetin is known to bind to alpha-tubulin and is a potent inhibitor of microtubule polymerization. Previous reports had identified that pironetin reacts with lysine-352 residue however analogues designed on this model had much lower potency, which was difficult to explain, hindering further development. We report crystallographic and mass spectrometric data that reveal that pironetin forms a covalent bond to cysteine-316 in alpha-tubulin via a Michael addition reaction. These data provide a basis for the rational design of alpha-tubulin targeting chemotherapeutics. Pironetin reacts covalently with cysteine-316 of alpha-tubulin to destabilize microtubule.,Yang J, Wang Y, Wang T, Jiang J, Botting CH, Liu H, Chen Q, Yang J, Naismith JH, Zhu X, Chen L Nat Commun. 2016 Jun 30;7:12103. doi: 10.1038/ncomms12103. PMID:27357539[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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