8a0l: Difference between revisions
New page: '''Unreleased structure''' The entry 8a0l is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Tubulin-CW1-complex== | |||
<StructureSection load='8a0l' size='340' side='right'caption='[[8a0l]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8a0l]] 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=8A0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A0L 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]] 1.9981Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=KLC:(3~{S},4~{R},8~{S},10~{S},12~{S},14~{S})-14-[(~{Z},4~{R})-4-(hydroxymethyl)hex-2-en-2-yl]-4,12-dimethoxy-9,9-dimethyl-3,8,10-tris(oxidanyl)-1-oxacyclotetradecan-2-one'>KLC</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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'>[https://proteopedia.org/fgij/fg.htm?mol=8a0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a0l OCA], [https://pdbe.org/8a0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a0l RCSB], [https://www.ebi.ac.uk/pdbsum/8a0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a0l ProSAT]</span></td></tr> | |||
</table> | |||
== 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 == | |||
Taxanes are microtubule-stabilizing agents used in the treatment of many solid tumors, but they often involve side effects affecting the peripheral nervous system. It has been proposed that this could be related to structural modifications on the filament upon drug binding. Alternatively, laulimalide and peloruside bind to a different site also inducing stabilization, but they have not been exploited in clinics. Here, we use a combination of the parental natural compounds and derived analogs to unravel the stabilization mechanism through this site. These drugs settle lateral interactions without engaging the M loop, which is part of the key and lock involved in the inter-protofilament contacts. Importantly, these drugs can modulate the angle between protofilaments, producing microtubules of different diameters. Among the compounds studied, we have found some showing low cytotoxicity and able to induce stabilization without compromising microtubule native structure. This opens the window of new applications for microtubule-stabilizing agents beyond cancer treatment. | |||
Chemical modulation of microtubule structure through the laulimalide/peloruside site.,Estevez-Gallego J, Alvarez-Bernad B, Pera B, Wullschleger C, Raes O, Menche D, Martinez JC, Lucena-Agell D, Prota AE, Bonato F, Bargsten K, Cornelus J, Gimenez-Abian JF, Northcote P, Steinmetz MO, Kamimura S, Altmann KH, Paterson I, Gago F, Van der Eycken J, Diaz JF, Oliva MA Structure. 2022 Nov 19:S0969-2126(22)00455-5. doi: 10.1016/j.str.2022.11.006. PMID:36462501<ref>PMID:36462501</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8a0l" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Gallus gallus]] | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Diaz JF]] | |||
[[Category: Oliva MA]] | |||
[[Category: Prota AE]] | |||
[[Category: Steinmetz MO]] | |||
Latest revision as of 16:36, 1 February 2024
Tubulin-CW1-complexTubulin-CW1-complex
Structural highlights
FunctionTBA1B_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. Publication Abstract from PubMedTaxanes are microtubule-stabilizing agents used in the treatment of many solid tumors, but they often involve side effects affecting the peripheral nervous system. It has been proposed that this could be related to structural modifications on the filament upon drug binding. Alternatively, laulimalide and peloruside bind to a different site also inducing stabilization, but they have not been exploited in clinics. Here, we use a combination of the parental natural compounds and derived analogs to unravel the stabilization mechanism through this site. These drugs settle lateral interactions without engaging the M loop, which is part of the key and lock involved in the inter-protofilament contacts. Importantly, these drugs can modulate the angle between protofilaments, producing microtubules of different diameters. Among the compounds studied, we have found some showing low cytotoxicity and able to induce stabilization without compromising microtubule native structure. This opens the window of new applications for microtubule-stabilizing agents beyond cancer treatment. Chemical modulation of microtubule structure through the laulimalide/peloruside site.,Estevez-Gallego J, Alvarez-Bernad B, Pera B, Wullschleger C, Raes O, Menche D, Martinez JC, Lucena-Agell D, Prota AE, Bonato F, Bargsten K, Cornelus J, Gimenez-Abian JF, Northcote P, Steinmetz MO, Kamimura S, Altmann KH, Paterson I, Gago F, Van der Eycken J, Diaz JF, Oliva MA Structure. 2022 Nov 19:S0969-2126(22)00455-5. doi: 10.1016/j.str.2022.11.006. PMID:36462501[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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