Abstract
In this study we report crystallization of Taxol in pure water, aqueous solutions containing tubulin proteins and tubulin-containing agarose gels. We show that crystallization of Taxol in tubulin-free aqueous solutions occurs by the formation of sheaf-like crystals, while in the presence of tubulin Taxol crystallizes in the form of spherulites. Whereas sheaves are characteristic for crystals formed by homogeneous nucleation, the spherical symmetry of the Taxol crystal formed in the presence of tubulin suggests they result from heterogeneous nucleation. To explain the formation of tubulin-Taxol nuclei we suggest a new, secondary Taxol-binding site within the tubulin heterodimer. Contrary to the known binding site, where the Taxol molecule is almost completely buried in the protein, the Taxol molecule in the secondary binding site is partially exposed to the solution and may serve as a bridge, connecting other Taxol molecules. Results presented in this work are important for in vivo and in vitro microtubule studies due to the possibility of mistaking these Taxol spherulites for microtubule asters, moreover a novel variable is proposed in the study of cells treated with Taxol for cancer treatment via sequestration of tubulin.
References
Mar 1, 1991·The Journal of Cell Biology·F VerdeE Karsenti
Aug 1, 1990·Journal of the National Cancer Institute·E K RowinskyR C Donehower
May 5, 1971·Journal of the American Chemical Society·M C WaniA T McPhail
Nov 1, 1995·The Journal of Cell Biology·T GaglioD A Compton
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·D MastropaoloN Camerman
Apr 13, 1995·The New England Journal of Medicine·E K Rowinsky, R C Donehower
Jan 1, 1997·Cell Motility and the Cytoskeleton·G Callaini, M G Riparbelli
Nov 26, 1998·Cell Motility and the Cytoskeleton·H Nilsson, M Wallin
Jan 8, 1999·Journal of Molecular Biology·D J RodiL Makowski
Apr 10, 1999·Molecular Biology of the Cell·A M YvonM A Jordan
Apr 15, 2000·The Journal of Biological Chemistry·M A DionneD A Compton
Jun 22, 2000·Cancer·T H WangY K Soong
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·J P SnyderE Nogales
May 19, 2001·International Immunopharmacology·J SzebeniY Talmon
Dec 18, 2001·Molecular Reproduction and Development·Q Y SunH Schatten
Apr 2, 2004·Nature Reviews. Cancer·Mary Ann Jordan, Leslie Wilson
May 8, 2004·International Journal of Pharmaceutics·Ruiwen Shi, Helen M Burt
Feb 1, 2007·The Journal of Physical Chemistry. B·Maurits C R HeijnaElias Vlieg
Sep 20, 2007·Expert Opinion on Drug Safety·Neena I MarupudiHenry Brem
Nov 28, 2007·Biomacromolecules·Kristin R Domike, Athene M Donald
Jan 24, 2008·PloS One·Margit FossDahong Zhang
Citations
Jun 16, 2011·PloS One·Andy MaloneySteven J Koch
Apr 9, 2014·PeerJ·Andy MaloneySteven J Koch
Nov 17, 2011·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Alina ShapiraYoav D Livney
Apr 12, 2016·Nano Today·Wang MaHonggang Cui
Sep 6, 2018·The Journal of Pharmacy and Pharmacology·Juan I PesoaLuciano N Mengatto
Nov 14, 2017·Chemistry of Materials : a Publication of the American Chemical Society·Minjee KangCecilia Leal