6jcj
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of crolibulin in complex with tubulin== | |
| + | <StructureSection load='6jcj' size='340' side='right'caption='[[6jcj]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6jcj]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JCJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JCJ 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=BG0:(4R)-2,7,8-triamino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-1-benzopyran-3-carbonitrile'>BG0</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=MG:MAGNESIUM+ION'>MG</scene></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=6jcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jcj OCA], [http://pdbe.org/6jcj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jcj RCSB], [http://www.ebi.ac.uk/pdbsum/6jcj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jcj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/TBA1B_PIG 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. [[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). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Microtubules (MTs) is one of the most important proteins in eukaryotic cells and plays a key role in the maintenance of cell morphology and cell division. The discovery and development of small molecule drugs targeting MTs has always been an important direction of anti-cancer research. Nowadays 4-Aryl-4H-chromenes have emerged as potent microtubule-targeting agents (MTAs) for various cancers. Crolibulin, a derivative of 4-Aryl-4H-chromenes, which has been progressed to Phase I/II clinical testing's for anaplastic thyroid cancer with the National Cancer Institute. However, the design and development of 4-Aryl-4H-chromenes family drugs have been hindered for a long time by the lack of structural information of the tubulin-agent complex. Here we report a 2.5A crystal structure of tubulin complexed with crolibulin. This complex structure reveals the interactions between crolibulin and tubulin, helps explain the results of the structure-activity-relationship (SAR) studies and provides a solid structural basis for the design and development of new 4-Aryl-4H-chromenes derivatives as MTAs. | ||
| - | + | Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design.,Zhang Z, Wang C, Ma L, Jiang X, Wu C, Wang Y, Jiang Y, Zheng W, Yang Y, Ma Y, Yang J Biochem Biophys Res Commun. 2019 Apr 2;511(2):381-386. doi:, 10.1016/j.bbrc.2019.02.064. Epub 2019 Feb 22. PMID:30803758<ref>PMID:30803758</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 6jcj" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Yang, J]] | [[Category: Yang, J]] | ||
| + | [[Category: Zhang, Z]] | ||
| + | [[Category: Cbsis]] | ||
| + | [[Category: Cell cycle]] | ||
| + | [[Category: Colchicine binding site inhibitor]] | ||
Revision as of 12:07, 13 March 2019
Structure of crolibulin in complex with tubulin
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