View source for 6gf3


==Tubulin-Jerantinine B acetate complex==
<StructureSection load='6gf3' size='340' side='right'caption='[[6gf3]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gf3]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GF3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GF3 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EX5:Jerantinine+B'>EX5</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></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=6gf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gf3 OCA], [http://pdbe.org/6gf3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gf3 RCSB], [http://www.ebi.ac.uk/pdbsum/6gf3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gf3 ProSAT]</span></td></tr>
</table>
== Function ==
[[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/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. [[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 ==
The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.

Sustainable Syntheses of (-)-Jerantinines A &amp; E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site.,Smedley CJ, Stanley PA, Qazzaz ME, Prota AE, Olieric N, Collins H, Eastman H, Barrow AS, Lim KH, Kam TS, Smith BJ, Duivenvoorden HM, Parker BS, Bradshaw TD, Steinmetz MO, Moses JE Sci Rep. 2018 Jul 13;8(1):10617. doi: 10.1038/s41598-018-28880-2. PMID:30006510<ref>PMID:30006510</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gf3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Barrow, A S]]
[[Category: Bradshaw, T D]]
[[Category: Collins, H]]
[[Category: Duivenvoorden, H M]]
[[Category: Eastman, H]]
[[Category: Kam, T S]]
[[Category: Lim, K H]]
[[Category: Moses, J E]]
[[Category: Olieric, N]]
[[Category: Parker, B S]]
[[Category: Prota, A E]]
[[Category: Qazzaz, M E]]
[[Category: Smedley, C J]]
[[Category: Smith, B J]]
[[Category: Stanley, P A]]
[[Category: Steinmetz, M O]]
[[Category: Cell cycle]]
[[Category: Cytoskeleton]]
[[Category: Microtubule]]
[[Category: Tubulin fold]]