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5fnv
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==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=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5fnv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] 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=5FNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FNV FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.61Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=5fnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fnv OCA], [https://pdbe.org/5fnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fnv RCSB], [https://www.ebi.ac.uk/pdbsum/5fnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fnv ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Molecules 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<ref>PMID:27357539</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5fnv" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Naismith | + | ==See Also== |
| - | [[Category: | + | *[[Stathmin-4 3D structures|Stathmin-4 3D structures]] |
| + | *[[Tubulin 3D Structures|Tubulin 3D Structures]] | ||
| + | *[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Gallus gallus]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Sus scrofa]] | ||
| + | [[Category: Naismith J]] | ||
| + | [[Category: Wang Y]] | ||
| + | [[Category: Zhu X]] | ||
Current revision
a new complex structure of tubulin with an alpha-beta unsaturated lactone
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