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Cited by 78Microtubule and mitosis dynamicsCancer Treatment and PharmacologySynthesis and biological activity

Structural insight into the stabilization of microtubules by taxanes

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Prota, Andrea E, Lucena-Agell, Daniel, Ma, Yuntao, Estevez-Gallego, Juan, Li, Shuo, Bargsten, Katja, Josa-Prado, Fernando, Altmann, Karl-Heinz +8 more·2023·eLife
DOI 10.7554/elife.84791PMC PMC10049219

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Abstract

Paclitaxel (Taxol) is a taxane and a chemotherapeutic drug that stabilizes microtubules. While the interaction of paclitaxel with microtubules is well described, the lack of high-resolution structural information on a tubulin-taxane complex precludes a comprehensive description of the binding determinants that affect its mechanism of action. Here, we solved the crystal structure of baccatin III the core moiety of paclitaxel-tubulin complex at 1.9 Å resolution. Based on this information, we engineered taxanes with modified C13 side chains, solved their crystal structures in complex with tubulin, and analyzed their effects on microtubules (X-ray fiber diffraction), along with those of paclitaxel, docetaxel, and baccatin III. Further comparison of high-resolution structures and microtubules’ diffractions with the apo forms and molecular dynamics approaches allowed us to understand the consequences of taxane binding to tubulin in solution and under assembled conditions. The results sheds light on three main mechanistic questions: (1) taxanes bind better to microtubules than to tubulin because tubulin assembly is linked to a βM-loopconformational reorganization (otherwise occludes the access to the taxane site) and, bulky C13 side chains preferentially recognize the assembled conformational state; (2) the occupancy of the taxane site has no influence on the straightness of tubulin protofilaments and; (3) longitudinal expansion of the microtubule lattices arises from the accommodation of the taxane core within the site, a process that is no related to the microtubule stabilization (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.

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  1. Adams PD Afonine PV Bunkóczi G Chen VB Davis IW Echols N Headd JJ Hung LW Kapral GJ Grosse-Kunstleve RW McCoy AJ Moriarty NW Oeffner R Read RJ Richardson DC Richardson JS Terwilliger TC Zwart PH 2010 PHENIX: A comprehensive python-based system for macromolecular structure solution Acta Crystallographica. Section D, Biological Crystallography 66 213 221 10.1107/S0907444909052925 20124702 PMC2815670 · DOI · Paper page
  2. Alushin GM Lander GC Kellogg EH Zhang R Baker D Nogales E 2014 High-Resolution microtubule structures reveal the structural transitions in αβ-tubulin upon GTP hydrolysis Cell 157 1117 1129 10.1016/j.cell.2014.03.053 24855948 PMC4054694 · DOI · Paper page
  3. Anandakrishnan R Aguilar B Onufriev AV 2012 H++ 3.0: Automating pk prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations Nucleic Acids Research 40 W537 W541 10.1093/nar/gks375 22570416 PMC3394296 · DOI
  4. Andreu JM Barasoain I 2001 The interaction of baccatin III with the taxol binding site of microtubules determined by a homogeneous assay with fluorescent taxoid Biochemistry 40 11975 11984 10.1021/bi010869+ 11580273 · DOI
  5. Andreu JM 2007 Microtubule protocols Totowa, NJ Humana Press
  6. Arbuck SG Dorr A Friedman MA 1994 Paclitaxel (Taxol) in breast cancer Hematology/Oncology Clinics of North America 8 121 140 10.1016/S0889-8588(18)30191-6 7908664 · DOI
  7. Arnal I Wade RH 1995 How does taxol stabilize microtubules? Current Biology 5 900 908 10.1016/s0960-9822(95)00180-1 7583148 · DOI
  8. Balaguer F Mühlethaler T Estévez-Gallego J Calvo E Giménez-Abián JF Risinger AL Sorensen EJ Vanderwal CD Altmann KH Mooberry SL Steinmetz MO Oliva MÁ Prota AE Díaz JF 2019 Crystal structure of the cyclostreptin-tubulin adduct: Implications for tubulin activation by taxane-site ligands International Journal of Molecular Sciences 20 1392 10.3390/ijms20061392 30897704 PMC6471726 · DOI
  9. Benoit MPMH Asenjo AB Sosa H 2018 Cryo-Em reveals the structural basis of microtubule depolymerization by kinesin-13s Nature Communications 9 1662 10.1038/s41467-018-04044-8 29695795 PMC5916938 · DOI
  10. Brabez N Lynch RM Xu L Gillies RJ Chassaing G Lavielle S Hruby VJ 2011 Design, synthesis, and biological studies of efficient multivalent melanotropin ligands: Tools toward melanoma diagnosis and treatment Journal of Medicinal Chemistry 54 7375 7384 10.1021/jm2009937 21928837 PMC3521580 · DOI
  11. Brunger AT Adams PD 2002 Molecular dynamics applied to X-ray structure refinement Accounts of Chemical Research 35 404 412 10.1021/ar010034r 12069625 · DOI
  12. Bueno O Estévez Gallego J Martins S Prota AE Gago F Gómez-SanJuan A Camarasa MJ Barasoain I Steinmetz MO Díaz JF Pérez-Pérez MJ Liekens S Priego EM 2018 High-affinity ligands of the colchicine domain in tubulin based on a structure-guided design Scientific Reports 8 4242 10.1038/s41598-018-22382-x 29523799 PMC5844890 · DOI
  13. Buey RM Díaz JF Andreu JM O’Brate A Giannakakou P Nicolaou KC Sasmal PK Ritzén A Namoto K 2004 Interaction of epothilone analogs with the paclitaxel binding site: Relationship between binding affinity, microtubule stabilization, and cytotoxicity Chemistry & Biology 11 225 236 10.1016/j.chembiol.2004.01.014 15123284 · DOI
  14. Canales A Rodríguez-Salarichs J Trigili C Nieto L Coderch C Andreu JM Paterson I Jiménez-Barbero J Díaz JF 2011 Insights into the interaction of discodermolide and docetaxel with tubulin: Mapping the binding sites of microtubule-stabilizing agents by using an integrated NMR and computational approach ACS Chemical Biology 6 789 799 10.1021/cb200099u 21539341 · DOI
  15. Canales A Nieto L Rodríguez-Salarichs J Sánchez-Murcia PA Coderch C Cortés-Cabrera A Paterson I Carlomagno T Gago F Andreu JM Altmann K-H Jiménez-Barbero J Díaz JF 2014 Molecular recognition of epothilones by microtubules and tubulin dimers revealed by biochemical and NMR approaches ACS Chemical Biology 9 1033 1043 10.1021/cb400673h 24524625 · DOI
  16. Carlier MF Pantaloni D 1983 Taxol effect on tubulin polymerization and associated guanosine 5’-triphosphate hydrolysis Biochemistry 22 4814 4822 10.1021/bi00289a031 6138095 · DOI
  17. Coderch C Tang Y Klett J Zhang SE Ma YT Shaorong W Matesanz R Pera B Canales A Jiménez-Barbero J Morreale A Díaz JF Fang WS Gago F 2013 A structure-based design of new C2- and C13-substituted taxanes: Tubulin binding affinities and extended quantitative structure-activity relationships using comparative binding energy (combine) analysis Organic & Biomolecular Chemistry 11 3046 3056 10.1039/c3ob40407b 23532250 · DOI
  18. Debs GE Cha M Liu X Huehn AR Sindelar CV 2020 Dynamic and asymmetric fluctuations in the microtubule wall captured by high-resolution cryoelectron microscopy PNAS 117 16976 16984 10.1073/pnas.2001546117 32636254 PMC7382274 · DOI
  19. Díaz JF Menéndez M Andreu JM 1993 Thermodynamics of ligand-induced assembly of tubulin Biochemistry 32 10067 10077 10.1021/bi00089a023 8104479 · DOI
  20. Díaz JF Valpuesta JM Chacón P Diakun G Andreu JM 1998 Changes in microtubule protofilament number induced by taxol binding to an easily accessible site: Internal microtubule dynamics The Journal of Biological Chemistry 273 33803 33810 10.1074/jbc.273.50.33803 9837970 · DOI
  21. Díaz JF Strobe R Engelborghs Y Souto AA Andreu JM 2000 Molecular recognition of taxol by microtubules: Kinetics and thermodynamics of binding of fluorescent taxol derivatives to an exposed site The Journal of Biological Chemistry 275 26265 26276 10.1074/jbc.M003120200 10818101 · DOI
  22. Elie-Caille C Severin F Helenius J Howard J Muller DJ Hyman AA 2007 Straight GDP-tubulin protofilaments form in the presence of taxol Current Biology 17 1765 1770 10.1016/j.cub.2007.08.063 17919908 · DOI
  23. Emsley P Lohkamp B Scott WG Cowtan K 2010 Features and development of coot Acta Crystallographica. Section D, Biological Crystallography 66 486 501 10.1107/S0907444910007493 20383002 PMC2852313 · DOI
  24. Estévez-Gallego J Josa-Prado F Ku S Buey RM Balaguer FA Prota AE Lucena-Agell D Kamma-Lorger C Yagi T Iwamoto H Duchesne L Barasoain I Steinmetz MO Chrétien D Kamimura S Díaz JF Oliva MA 2020 Structural model for differential cap maturation at growing microtubule ends eLife 9 e50155 10.7554/eLife.50155 32151315 PMC7064335 · DOI · Paper page
  25. Ettinger DS 1993 Taxol in the treatment of lung cancer Journal of the National Cancer Institute. Monographs 15 177 179 7912523
  26. Field JJ Pera B Calvo E Canales A Zurwerra D Trigili C Rodríguez-Salarichs J Matesanz R Kanakkanthara A Wakefield SJ Singh AJ Jiménez-Barbero J Northcote P Miller JH López JA Hamel E Barasoain I Altmann K-H Díaz JF 2012 Zampanolide, a potent new microtubule-stabilizing agent, covalently reacts with the taxane luminal site in tubulin α, β-heterodimers and microtubules Chemistry & Biology 19 686 698 10.1016/j.chembiol.2012.05.008 22726683 PMC3383615 · DOI
  27. Field JJ Díaz JF Miller JH 2013 The binding sites of microtubule-stabilizing agents Chemistry & Biology 20 301 315 10.1016/j.chembiol.2013.01.014 23521789 · DOI
  28. Gornstein E Schwarz TL 2014 The paradox of paclitaxel neurotoxicity: mechanisms and unanswered questions Neuropharmacology 76 Pt A 175 183 10.1016/j.neuropharm.2013.08.016 23978385 · DOI
  29. Howard WD Timasheff SN 1988 Linkages between the effects of taxol, colchicine, and GTP on tubulin polymerization The Journal of Biological Chemistry 263 1342 1346 2891710
  30. Hyman AA Salser S Drechsel DN Unwin N Mitchison TJ 1992 Role of GTP hydrolysis in microtubule dynamics: information from a slowly hydrolyzable analogue, GMPCPP Molecular Biology of the Cell 3 1155 1167 10.1091/mbc.3.10.1155 1421572 PMC275679 · DOI
  31. Kabsch W 2010 XDS Acta Crystallographica. Section D, Biological Crystallography 66 125 132 10.1107/S0907444909047337 20124692 PMC2815665 · DOI · Paper page
  32. Kamimura S Fujita Y Wada Y Yagi T Iwamoto H 2016 X-ray fiber diffraction analysis shows dynamic changes in axial tubulin repeats in native microtubules depending on paclitaxel content, temperature and GTP-hydrolysis Cytoskeleton 73 131 144 10.1002/cm.21283 26873786 · DOI
  33. Kellogg EH Hejab NMA Howes S Northcote P Miller JH Díaz JF Downing KH Nogales E 2017 Insights into the distinct mechanisms of action of taxane and non-taxane microtubule stabilizers from cryo-EM structures Journal of Molecular Biology 429 633 646 10.1016/j.jmb.2017.01.001 28104363 PMC5325780 · DOI · Paper page
  34. Kingston DG 2000 Recent advances in the chemistry of taxol Journal of Natural Products 63 726 734 10.1021/np000064n 10843603 · DOI
  35. Klett J Núñez-Salgado A Dos Santos HG Cortés-Cabrera Á Perona A Gil-Redondo R Abia D Gago F Morreale A 2012 MM-ISMSA: An ultrafast and accurate scoring function for protein-protein docking Journal of Chemical Theory and Computation 8 3395 3408 10.1021/ct300497z 26605745 · DOI
  36. Knossow M Campanacci V Khodja LA Gigant B 2020 The mechanism of tubulin assembly into microtubules: Insights from structural studies IScience 23 101511 10.1016/j.isci.2020.101511 32920486 PMC7491153 · DOI
  37. Lataste H Senilh V Wright M Guénard D Potier P 1984 Relationships between the structures of taxol and baccatine III derivatives and their in vitro action on the disassembly of mammalian brain and physarum amoebal microtubules PNAS 81 4090 4094 10.1073/pnas.81.13.4090 6146136 PMC345374 · DOI
  38. Le Grand S Götz AW Walker RC 2013 SPFP: Speed without compromise—A mixed precision model for GpU accelerated molecular dynamics simulations Computer Physics Communications 184 374 380 10.1016/j.cpc.2012.09.022 · DOI
  39. Li Y Edsall R Jr Jagtap PG Kingston DG Bane S 2000 Equilibrium studies of a fluorescent paclitaxel derivative binding to microtubules Biochemistry 39 616 623 10.1021/bi992044u 10642187 · DOI
  40. Lindemann K Christensen RD Vergote I Stuart G Izquierdo MA Kærn J Havsteen H Eisenhauer E Ridderheim M Lopez AB Hirte H Aavall-Lundquvist E Vrdoljak E Green J Kristensen GB 2012 First-Line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (Tec versus TC) -- a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG Annals of Oncology 23 2613 2619 10.1093/annonc/mds060 22539562 · DOI
  41. Löwe J Li H Downing KH Nogales E 2001 Refined structure of alpha beta-tubulin at 3.5 A resolution Journal of Molecular Biology 313 1045 1057 10.1006/jmbi.2001.5077 11700061 · DOI
  42. Ludueña RF Banerjee A 2008 The role of microtubules Fojo T Cell Biology, Neurobiology, and Oncology Totowa, NJ Humana Press 123 175
  43. Ma Y-T Yang Y Cai P Sun D-Y Sánchez-Murcia PA Zhang X-Y Jia W-Q Lei L Guo M Gago F Wang H Fang W-S 2018 A series of enthalpically optimized docetaxel analogues exhibiting enhanced antitumor activity and water solubility Journal of Natural Products 81 524 533 10.1021/acs.jnatprod.7b00857 29359935 · DOI
  44. Maier JA Martinez C Kasavajhala K Wickstrom L Hauser KE Simmerling C 2015 Ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99sb Journal of Chemical Theory and Computation 11 3696 3713 10.1021/acs.jctc.5b00255 26574453 PMC4821407 · DOI
  45. Manka SW Moores CA 2018 The role of tubulin-tubulin lattice contacts in the mechanism of microtubule dynamic instability Nature Structural & Molecular Biology 25 607 615 10.1038/s41594-018-0087-8 29967541 PMC6201834 · DOI · Paper page
  46. Matesanz R Barasoain I Yang CG Wang L Li X de Inés C Coderch C Gago F Barbero JJ Andreu JM Fang WS Díaz JF 2008 Optimization of taxane binding to microtubules: Binding affinity dissection and incremental construction of a high-affinity analog of paclitaxel Chemistry & Biology 15 573 585 10.1016/j.chembiol.2008.05.008 18559268 · DOI
  47. Morreale A Gil-Redondo R Ortiz AR 2007 A new implicit solvent model for protein-ligand docking Proteins 67 606 616 10.1002/prot.21269 17330937 · DOI
  48. Nawrotek A Knossow M Gigant B 2011 The determinants that govern microtubule assembly from the atomic structure of GTP-tubulin Journal of Molecular Biology 412 35 42 10.1016/j.jmb.2011.07.029 21787788 · DOI
  49. Nogales E Wolf SG Downing KH 1998 Structure of the alpha beta tubulin dimer by electron crystallography Nature 391 199 203 10.1038/34465 9428769 · DOI
  50. Nogales E Whittaker M Milligan RA Downing KH 1999 High-Resolution model of the microtubule Cell 96 79 88 10.1016/s0092-8674(00)80961-7 9989499 · DOI
  51. Ojima I Duclos O Dormán G Simonot B Prestwich GD Rao S Lerro KA Horwitz SB 1995 A new paclitaxel photoaffinity analog with A 3- (4-benzoylphenyl) propanoyl probe for characterization of drug-binding sites on tubulin and P-glycoprotein Journal of Medicinal Chemistry 38 3891 3894 10.1021/jm00020a001 7562921 · DOI
  52. Parness J Kingston DGI Powell RG Harracksingh C Horwitz SB 1982 Structure-Activity study of cytotoxicity and microtubule assembly in vitro by taxol and related taxanes Biochemical and Biophysical Research Communications 105 1082 1089 10.1016/0006-291x(82)91080-4 6124250 · DOI
  53. Pecqueur L Duellberg C Dreier B Jiang Q Wang C Plückthun A Surrey T Gigant B Knossow M 2012 A designed ankyrin repeat protein selected to bind to tubulin caps the microtubule plus end PNAS 109 12011 12016 10.1073/pnas.1204129109 22778434 PMC3409770 · DOI
  54. Prota AE Bargsten K Zurwerra D Field JJ Díaz JF Altmann KH Steinmetz MO 2013a Molecular mechanism of action of microtubule-stabilizing anticancer agents Science 339 587 590 10.1126/science.1230582 23287720 · DOI
  55. Prota AE Magiera MM Kuijpers M Bargsten K Frey D Wieser M Jaussi R Hoogenraad CC Kammerer RA Janke C Steinmetz MO 2013b Structural basis of tubulin tyrosination by tubulin tyrosine ligase The Journal of Cell Biology 200 259 270 10.1083/jcb.201211017 23358242 PMC3563685 · DOI
  56. Prota AE Bargsten K Redondo-Horcajo M Smith AB Yang CPH McDaid HM Paterson I Horwitz SB Fernando Díaz J Steinmetz MO 2017 Structural basis of microtubule stabilization by discodermolide Chembiochem 18 905 909 10.1002/cbic.201600696 28207984 PMC5559732 · DOI
  57. Ram RN Meher NK 2000 A simple method for the preparation of monomethyl esters of dicarboxylic acids by selective esterification of the nonconjugated carboxyl group in the presence of an aromatic or conjugated carboxyl group Journal of Chemical Research 2000 282 283 10.3184/030823400103167309 · DOI
  58. Rodríguez-Barrios F Balzarini J Gago F 2005 The molecular basis of resilience to the effect of the lys103asn mutation in non-nucleoside HIV-1 reverse transcriptase inhibitors studied by targeted molecular dynamics simulations Journal of the American Chemical Society 127 7570 7578 10.1021/ja042289g 15898808 · DOI
  59. Roe DR Cheatham TE 2013 PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data Journal of Chemical Theory and Computation 9 3084 3095 10.1021/ct400341p 26583988 · DOI
  60. Ryckaert JP Ciccotti G Berendsen HJC 1977 Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes J Comput Phys 23 327 341 10.1016/0021-9991(77)90098-5 · DOI
  61. Sáez-Calvo G Sharma A Balaguer F Barasoain I Rodríguez-Salarichs J Olieric N Muñoz-Hernández H Berbís MÁ Wendeborn S Peñalva MA Matesanz R Canales Á Prota AE Jímenez-Barbero J Andreu JM Lamberth C Steinmetz MO Díaz JF 2017 Triazolopyrimidines are microtubule-stabilizing agents that bind the vinca inhibitor site of tubulin Cell Chemical Biology 24 737 750 10.1016/j.chembiol.2017.05.016 28579361 · DOI
  62. Salomon-Ferrer R Götz AW Poole D Le Grand S Walker RC 2013 Routine microsecond molecular dynamics simulations with amber on GPUs. 2. explicit solvent particle mesh ewald Journal of Chemical Theory and Computation 9 3878 3888 10.1021/ct400314y 26592383 · DOI
  63. Samaranayake G Neidigh KA Kingston DGI 1993 Modified taxols, 8. deacylation and reacylation of baccatin III Journal of Natural Products 56 884 898 10.1021/np50096a012 8102392 · DOI
  64. Sánchez-Murcia PA Mills A Cortés-Cabrera Á Gago F 2019 Unravelling the covalent binding of zampanolide and taccalonolide AJ to a minimalist representation of a human microtubule Journal of Computer-Aided Molecular Design 33 627 644 10.1007/s10822-019-00208-w 31152293 · DOI
  65. Saville MW Lietzau J Pluda JM Feuerstein I Odom J Wilson WH Humphrey RW Feigal E Steinberg SM Broder S 1995 Treatment of HIV-associated kaposi’s sarcoma with paclitaxel Lancet 346 26 28 10.1016/s0140-6736(95)92654-2 7603142 · DOI
  66. Scalmani G Frisch MJ 2010 Continuous surface charge polarizable continuum models of solvation. I. General formalism J Chem Phys 132 114110 10.1063/1.3359469 20331284 · DOI
  67. Schiff PB Horwitz SB 1981 Taxol assembles tubulin in the absence of exogenous guanosine 5’-triphosphate or microtubule-associated proteins Biochemistry 20 3247 3252 10.1021/bi00514a041 6113842 · DOI
  68. Snyder JP Nettles JH Cornett B Downing KH Nogales E 2001 The binding conformation of taxol in beta-tubulin: a model based on electron crystallographic density PNAS 98 5312 5316 10.1073/pnas.051309398 11309480 PMC33206 · DOI
  69. Steinmetz MO Prota AE 2018 Microtubule-Targeting agents: Strategies to hijack the cytoskeleton Trends in Cell Biology 28 776 792 10.1016/j.tcb.2018.05.001 29871823 · DOI
  70. Trigili C Barasoain I Sánchez-Murcia PA Bargsten K Redondo-Horcajo M Nogales A Gardner NM Meyer A Naylor GJ Gómez-Rubio E Gago F Steinmetz MO Paterson I Prota AE Díaz JF 2016 Structural determinants of the dictyostatin chemotype for tubulin binding affinity and antitumor activity against taxane- and epothilone-resistant cancer cells ACS Omega 1 1192 1204 10.1021/acsomega.6b00317 30023505 PMC6044705 · DOI
  71. Vale RD Coppin CM Malik F Kull FJ Milligan RA 1994 Tubulin GTP hydrolysis influences the structure, mechanical properties, and kinesin-driven transport of microtubules The Journal of Biological Chemistry 269 23769 23775 7916345
  72. Wang J Cieplak P Kollman PA 2000 How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? Journal of Computational Chemistry 21 1049 1074 10.1002/1096-987X(200009)21:12<1049::AID-JCC3>3.0.CO;2-F · DOI
  73. Wang J Wolf RM Caldwell JW Kollman PA Case DA 2004 Development and testing of a general amber force field Journal of Computational Chemistry 25 1157 1174 10.1002/jcc.20035 15116359 · DOI
  74. Yajima H Ogura T Nitta R Okada Y Sato C Hirokawa N 2012 Conformational changes in tubulin in GMPCPP and GDP-taxol microtubules observed by cryoelectron microscopy The Journal of Cell Biology 198 315 322 10.1083/jcb.201201161 22851320 PMC3413364 · DOI

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Authors
Prota, A. E., Lucena-Agell, D., Ma, Y., Estevez-Gallego, J., Li, S., Bargsten, K., Josa-Prado, F., Altmann, K.-H., Gaillard, N., Kamimura, S., Mühlethaler, T., Gago, F., Oliva, M. A., Steinmetz, M. O., Fang, W.-S., & Díaz, J. F.
Affiliations
  • Paul Scherrer Institute (CH)
  • Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • ETH Zurich (CH)
  • Chuo University (JP)
  • Universidad de Alcalá (ES)
  • University of Basel (CH)
  • Consejo Superior de Investigaciones Científicas (ES)
Corresponding author
  • Prota, Andrea E
  • Fang, Wei-Shuo
  • Díaz, J Fernando
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2023-03-06
Volume
12
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.84791
PMC
PMC10049219
OpenAlex
W4323294518
Cited by
78
References
2
Citations by year
2026: 34 · 2025: 21 · 2024: 16 · 2023: 7
FWCI
10.89
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection
Funders
  • Ministerio de Ciencia e Innovación (PID2019-104545RB-I00 (AEI/10.13039/501100011033), PID2019-104070RB-C22 (AEI/10.13039/501100011033))
  • Consejo Superior de Investigaciones Científicas (PIE 201920E111)
  • Fundación Tatiana Pérez de Guzmán el Bueno (Proyecto de Investigación en Neurociencia 2020)
  • European Union NextGenerationEU (H2020-MSCA-ITN-2019 860070 TUBINTRAIN)
  • Swiss National Science Foundation (310030_192566)
  • JSPS KAKENHI (16K07328/17H03668)
  • National Natural Science Foundation of China (30930108)
  • Chinese Academy of Medical Sciences (2016-I2M-1-010)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords
taxanes, paclitaxel, baccatin III, tubulin, microtubule stabilization, docetaxel, X-ray fiber diffraction
MeSH terms
Alkaloids, Bridged-Ring Compounds, Microtubules, Tubulin, Paclitaxel, Taxoids

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