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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8bdf]] 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=8BDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BDF FirstGlance]. <br>
<table><tr><td colspan='2'>[[8bdf]] 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=8BDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BDF FirstGlance]. <br>
</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=R42:[(1~{S},2~{S},3~{R},4~{S},7~{R},9~{S},10~{S},12~{R},15~{S})-4-acetyloxy-15-[(2~{R},3~{S})-3-[(4-methoxy-2-methylidene-4-oxidanylidene-butanoyl)amino]-2-oxidanyl-3-phenyl-propanoyl]oxy-10,14,16,16-tetramethyl-1,9,12-tris(oxidanyl)-11-oxidanylidene-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl]+benzoate'>R42</scene></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]] 1.95&#8491;</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=R42:[(1~{S},2~{S},3~{R},4~{S},7~{R},9~{S},10~{S},12~{R},15~{S})-4-acetyloxy-15-[(2~{R},3~{S})-3-[(4-methoxy-2-methylidene-4-oxidanylidene-butanoyl)amino]-2-oxidanyl-3-phenyl-propanoyl]oxy-10,14,16,16-tetramethyl-1,9,12-tris(oxidanyl)-11-oxidanylidene-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl]+benzoate'>R42</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=8bdf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bdf OCA], [https://pdbe.org/8bdf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bdf RCSB], [https://www.ebi.ac.uk/pdbsum/8bdf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bdf ProSAT]</span></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=8bdf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bdf OCA], [https://pdbe.org/8bdf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bdf RCSB], [https://www.ebi.ac.uk/pdbsum/8bdf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bdf 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.
[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.
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== Publication Abstract from PubMed ==
Paclitaxel (Taxol((R))) is a taxane and a first-line chemotherapeutic drug that stabilizes microtubules. While the interaction of paclitaxel with microtubules is well described, the current lack of high-resolution structural information on a tubulin-taxane complex precludes a comprehensive description of the binding determinants that affect the drug's mechanism of action. Here, we solved the crystal structure of the core baccatin III moiety of paclitaxel lacking the C13 side chain in complex with tubulin at 1.9 A resolution. Based on this information, we engineered two tailor-made taxanes with modified C13 side chains, solved their crystal structures in complex with tubulin, and analyzed their effects along with those of paclitaxel, docetaxel, and baccatin III on the microtubule lattice by X-ray fiber diffraction. We then compared high-resolution structures of ligand-bound tubulin and microtubule complexes with apo forms and used molecular dynamics simulations to understand the consequences of taxane binding to tubulin as well as to simplified protofilament and microtubule-lattice models. Our combined approach sheds light on three mechanistic questions. Firstly, taxanes bind better to microtubules as compared to unassembled tubulin due to a dual structural mechanism: Tubulin assembly is linked to a conformational reorganization of the bM loop, which otherwise occludes ligand access to the taxane site, while the bulky C13 side chains preferentially recognize the microtubule-assembled over the unassembled conformational state of tubulin. Second, the occupancy of the taxane site by a ligand has no influence on the straightness of tubulin protofilaments. Finally, the longitudinal expansion of the microtubule lattices arises from the accommodation of the taxane core within the site, a process that is, however, not related to the microtubule stabilization mechanism of taxanes, as all analogs tested expand the microtubule lattice, despite the fact that one of them, Baccatin III, is biochemically inactive. In conclusion, our combined experimental and computational approach allowed us to describe the tubulin-taxane interaction in atomic detail and assess the structural determinants for binding.


Structural insight into the stabilization of microtubules by taxanes.,Prota AE, Lucena-Agell D, Ma Y, Estevez-Gallego J, Li S, Bargsten K, Josa-Prado F, Altmann KH, Gaillard N, Kamimura S, Muhlethaler T, Gago F, Oliva MA, Steinmetz MO, Fang WS, Diaz JF Elife. 2023 Mar 6;12:e84791. doi: 10.7554/eLife.84791. PMID:36876916<ref>PMID:36876916</ref>
==See Also==
 
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
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<div class="pdbe-citations 8bdf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
</StructureSection>

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