View source for 5ng1


==TUBULIN-MTC-zampanolide complex==
<StructureSection load='5ng1' size='340' side='right'caption='[[5ng1]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ng1]] 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=5NG1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NG1 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8WB:2-methoxy-5-(2,3,4-trimethoxyphenyl)cyclohepta-2,4,6-trien-1-one'>8WB</scene>, <scene name='pdbligand=8WE:(2~{Z},4~{E})-~{N}-[(~{S})-oxidanyl-[(1~{S},2~{E},5~{S},11~{R},17~{S},19~{R})-3,11,19-trimethyl-7,13-bis(oxidanylidene)-6,21-dioxabicyclo[15.3.1]henicos-2-en-5-yl]methyl]hexa-2,4-dienamide'>8WE</scene>, <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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZPN:(2Z,4E)-N-[(S)-[(1S,2E,5S,8E,10Z,17S)-3,11-DIMETHYL-19-METHYLIDENE-7,13-DIOXO-6,21-DIOXABICYCLO[15.3.1]HENICOSA-2,8,10-TRIEN-5-YL](HYDROXY)METHYL]HEXA-2,4-DIENAMIDE'>ZPN</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=5ng1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ng1 OCA], [https://pdbe.org/5ng1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ng1 RCSB], [https://www.ebi.ac.uk/pdbsum/5ng1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ng1 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 ==
The marine natural product zampanolide and analogues thereof constitute a new chemotype of taxoid site microtubule-stabilizing agents with a covalent mechanism of action. Zampanolide-ligated tubulin has the switch-activation loop (M-loop) in the assembly prone form and, thus, represents an assembly activated state of the protein. In this study, we have characterized the biochemical properties of the covalently modified, activated tubulin dimer, and we have determined the effect of zampanolide on tubulin association and the binding of tubulin ligands at other binding sites. Tubulin activation by zampanolide does not affect its longitudinal oligomerization but does alter its lateral association properties. The covalent binding of zampanolide to beta-tubulin affects both the colchicine site, causing a change of the quantum yield of the bound ligand, and the exchangeable nucleotide binding site, reducing the affinity for the nucleotide. While these global effects do not change the binding affinity of 2-methoxy-5-(2,3,4-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MTC) (a reversible binder of the colchicine site), the binding affinity of a fluorescent analogue of GTP (Mant-GTP) at the nucleotide E-site is reduced from 12 +/- 2 x 105 M-1 in the case of unmodified tubulin to 1.4 +/- 0.3 x 105 M-1 in the case of the zampanolide tubulin adduct, indicating signal transmission between the taxane site and the colchicine and nucleotide sites of beta-tubulin.

Zampanolide Binding to Tubulin Indicates Cross-Talk of Taxane Site with Colchicine and Nucleotide Sites.,Field JJ, Pera B, Gallego JE, Calvo E, Rodriguez-Salarichs J, Saez-Calvo G, Zuwerra D, Jordi M, Andreu JM, Prota AE, Menchon G, Miller JH, Altmann KH, Diaz JF J Nat Prod. 2017 Oct 12. doi: 10.1021/acs.jnatprod.7b00704. PMID:29023132<ref>PMID:29023132</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ng1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
*[[Tubulin tyrosine ligase 3D structures|Tubulin tyrosine ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Altmann K-H]]
[[Category: Calvo E]]
[[Category: Diaz JF]]
[[Category: Estevez Gallego J]]
[[Category: Field JJ]]
[[Category: Jordi M]]
[[Category: Menchon G]]
[[Category: Miller JH]]
[[Category: Pera B]]
[[Category: Prota AE]]
[[Category: Rodriguez-Salarichs J]]
[[Category: Saez-Calvo G]]
[[Category: Zuwerra D]]