6xes
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Tubulin-RB3_SLD in complex with compound 40a== |
| - | <StructureSection load='6xes' size='340' side='right'caption='[[6xes]]' scene=''> | + | <StructureSection load='6xes' size='340' side='right'caption='[[6xes]], [[Resolution|resolution]] 2.32Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6xes]] is a 5 chain structure with sequence from [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=6XES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XES FirstGlance]. <br> |
| - | </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=6xes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xes OCA], [https://pdbe.org/6xes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xes RCSB], [https://www.ebi.ac.uk/pdbsum/6xes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xes ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.32Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TU3:[6-(3-hydroxy-4-methylphenyl)pyrazin-2-yl](3,4,5-trimethoxyphenyl)methanone'>TU3</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=6xes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xes OCA], [https://pdbe.org/6xes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xes RCSB], [https://www.ebi.ac.uk/pdbsum/6xes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xes ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We previously reported a potent tubulin inhibitor CH-2-77. In this study, we optimized the structure of CH-2-77 by blocking metabolically labile sites and synthesized a series of CH-2-77 analogues. Two compounds, 40a and 60c, preserved the potency while improving the metabolic stability over CH-2-77 by 3- to 4-fold (46.8 and 29.4 vs 10.8 min in human microsomes). We determined the high-resolution X-ray crystal structures of 40a (resolution 2.3 A) and 60c (resolution 2.6 A) in complex with tubulin and confirmed their direct binding at the colchicine-binding site. In vitro, 60c maintained its mode of action by inhibiting tubulin polymerization and was effective against P-glycoprotein-mediated multiple drug resistance and taxol resistance. In vivo, 60c exhibited a strong inhibitory effect on tumor growth and metastasis in a taxol-resistant A375/TxR xenograft model without obvious toxicity. Collectively, this work showed that 60c is a promising lead compound for further development as a potential anticancer agent. | ||
| + | |||
| + | Design, Synthesis, and Biological Evaluation of Stable Colchicine-Binding Site Tubulin Inhibitors 6-Aryl-2-benzoyl-pyridines as Potential Anticancer Agents.,Chen H, Deng S, Albadari N, Yun MK, Zhang S, Li Y, Ma D, Parke DN, Yang L, Seagroves TN, White SW, Miller DD, Li W J Med Chem. 2021 Aug 26;64(16):12049-12074. doi: 10.1021/acs.jmedchem.1c00715. , Epub 2021 Aug 11. PMID:34378386<ref>PMID:34378386</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6xes" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Stathmin-4 3D structures|Stathmin-4 3D structures]] | ||
| + | *[[Tubulin 3D Structures|Tubulin 3D Structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Rattus norvegicus]] |
| + | [[Category: Sus scrofa]] | ||
| + | [[Category: White SW]] | ||
| + | [[Category: Yun M]] | ||
Current revision
Tubulin-RB3_SLD in complex with compound 40a
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