6fjf
From Proteopedia
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==Tubulin-FcMaytansine complex== | ==Tubulin-FcMaytansine complex== | ||
| - | <StructureSection load='6fjf' size='340' side='right' caption='[[6fjf]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='6fjf' size='340' side='right'caption='[[6fjf]], [[Resolution|resolution]] 2.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6fjf]] is a 6 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[6fjf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FJF 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 | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.402Å</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=DMS:DIMETHYL+SULFOXIDE'>DMS</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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fjf OCA], [https://pdbe.org/6fjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fjf RCSB], [https://www.ebi.ac.uk/pdbsum/6fjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fjf ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://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. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on beta-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer. | ||
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| + | A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.,Menchon G, Prota AE, Lucena-Agell D, Bucher P, Jansen R, Irschik H, Muller R, Paterson I, Diaz JF, Altmann KH, Steinmetz MO Nat Commun. 2018 May 29;9(1):2106. doi: 10.1038/s41467-018-04535-8. PMID:29844393<ref>PMID:29844393</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6fjf" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Stathmin-4 3D structures|Stathmin-4 3D structures]] | ||
| + | *[[Tubulin 3D Structures|Tubulin 3D Structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
| - | [[Category: | + | [[Category: Gallus gallus]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Rattus norvegicus]] |
| - | [[Category: | + | [[Category: Altmann K-H]] |
| - | [[Category: | + | [[Category: Bucher P]] |
| - | [[Category: | + | [[Category: Diaz JF]] |
| - | [[Category: | + | [[Category: Lucena Angell D]] |
| - | [[Category: | + | [[Category: Menchon G]] |
| - | [[Category: | + | [[Category: Mueller R]] |
| - | [[Category: | + | [[Category: Paterson I]] |
| - | [[Category: | + | [[Category: Prota AE]] |
| - | [[Category: | + | [[Category: Steinmetz MO]] |
| - | + | ||
Current revision
Tubulin-FcMaytansine complex
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