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Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding sites
Abstract
Cyclostreptin (1), a natural product from Streptomyces sp. 9885, irreversibly stabilizes cellular microtubules, causes cell cycle arrest, evades drug resistance mediated by P-glycoprotein in a tumor cell line and potently inhibits paclitaxel binding to microtubules, yet it only weakly induces tubulin assembly. In trying to understand this paradox, we observed irreversible binding of synthetic cyclostreptin to tubulin. This results from formation of covalent crosslinks to beta-tubulin in cellular microtubules and microtubules formed from purified tubulin in a 1:1 total stoichiometry distributed between Thr220 (at the outer surface of a pore in the microtubule wall) and Asn228 (at the lumenal paclitaxel site). Unpolymerized tubulin was only labeled at Thr220. Thus, the pore region of beta-tubulin is an undescribed binding site that (i) elucidates the mechanism by which taxoid-site compounds reach the kinetically unfavorable lumenal site and (ii) explains how taxoid-site drugs induce microtubule formation from dimeric and oligomeric tubulin.
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“These nucleophilic centers are also present in DNA and other biologically relevant compounds, such as glutathione.116–121”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [119]
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Cites
Microtubules as a target for anticancer drugs
Jordan, M. A., & Wilson, L. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1317 · Cited by 4,000
Promotion of microtubule assembly in vitro by taxol
SCHIFF, P. B., FANT, J., & HORWITZ, S. B. (1979) · Nature · doi:10.1038/277665a0 · Cited by 3,600
Structure of the αβ tubulin dimer by electron crystallography
Nogales, E., Wolf, S., & Downing, K. (1998) · Nature · doi:10.1038/34465 · Cited by 1,623
High-Resolution Model of the Microtubule
Nogales, E., Whittaker, M., Milligan, R. A., & Downing, K. H. (1999) · Cell · doi:10.1016/s0092-8674(00)80961-7 · Cited by 1,200
Colchicine-binding protein of mammalian brain and its relation to microtubules
Weisenberg, R. C., Broisy, G. G., & Taylor, E. W. (1968) · Biochemistry · doi:10.1021/bi00852a043 · Cited by 1,161
Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations.
Jordan, M. A., Toso, R. J., Thrower, D., & Wilson, L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9552 · Cited by 1,095
Evans, D. C., Watt, A. P., Nicoll‐Griffith, D. A., & Baillie, T. A. (2003) · Chemical Research in Toxicology · doi:10.1021/tx034170b · Cited by 708
Giannakakou, P., Sackett, D. L., Kang, Y., Zhan, Z., Buters, J., Fojo, T., & Poruchynsky, M. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.27.17118 · Cited by 682
Taxol binds to polymerized tubulin in vitro
Parness, J., & Horwitz, S. (1981) · The Journal of Cell Biology · doi:10.1083/jcb.91.2.479 · Cited by 624
Barshop, B. A., Wrenn, R. F., & Frieden, C. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90660-7 · Cited by 597
Research works printed but not linked: 1
- Buey R.M., 2004, Chem. Biol., 11, 225
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Kubíček, K., Grimm, S. K., Orts, J., Sasse, F., & Carlomagno, T. (2010) · Angewandte Chemie · doi:10.1002/ange.200906828 · Cited by 11
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Calvo, E., Camafeita, E., Díaz, J. F., & López, J. A. (2008) · Current Proteomics · doi:10.2174/157016408783955128 · Cited by 11
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Ojima, I., Kamath, A., & Seitz, J. D. (2014) · Methods and principles in medicinal chemistry · doi:10.1002/9783527676545.ch04 · Cited by 9
Molecular Modeling of Block Copolymer Self‐Assembly and Micellar Drug Delivery
Kang, M., Lam, D., Discher, D. E., & Loverde, S. M. (2015) · Wiley eBooks · doi:10.1002/9781118573983.ch4 · Cited by 9
Cardá, M., Murga, J., Díaz‐Oltra, S., García-Pla, J., Paños, J., Falomir, E., Trigili, C., Díaz, J. F., Barasoaı́n, I., & Marco, J. A. (2013) · European Journal of Organic Chemistry · doi:10.1002/ejoc.201201283 · Cited by 8
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Andres, A. E., Rane, D., & Peterson, B. R. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-1983-4_28 · Cited by 8
Takahashi‐Ruiz, L., Morris, J. D., Crews, P., Johnson, T. A., & Risinger, A. L. (2022) · Molecules · doi:10.3390/molecules27134244 · Cited by 8
Lee, M. M., Gao, Z., & Peterson, B. R. (2017) · Angewandte Chemie · doi:10.1002/ange.201703298 · Cited by 8
Zhang, W., Yang, L., Si, W., Tang, M., Bai, P., Zhu, Z., Kuang, S., Liu, J., Shi, M., Huang, J., et al. (2022) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.106053 · Cited by 8
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Andres, A. E., Mariano, A., Rane, D., & Peterson, B. R. (2022) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.2c00031 · Cited by 7
Cardá, M., Murga, J., Panos, J., Angulo‐Pachón, C. A., García-Pla, J., Díaz‐Oltra, S., Marco, J. A., Trigili, C., Redondo‐Horcajo, M., Díaz, J. F., et al. (2013) · Current Medicinal Chemistry · doi:10.2174/0929867311320090006 · Cited by 7
Self-citationPotential phytochemicals as microtubule-disrupting agents in cancer prevention
Mir, S. A., Padhiary, A., Pati, A., Tete, S. S., Meher, R. K., Baitharu, I., Muhammad, A., & Nayak, B. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-19143-5.00020-7 · Cited by 7
Microtubules as a Target in Cancer Therapy
Risinger, A. L., & Mooberry, S. L. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-788-0_11 · Cited by 5
Tanaka, N., Suzuki, T., Matsumura, T., Hosoya, Y., & Nakada, M. (2009) · Angewandte Chemie · doi:10.1002/ange.200900097 · Cited by 5
Antimicrotubule Agents That Bind Covalently to Tubulin
Sackett, D. L. (2009) · Humana Press eBooks · doi:10.1007/978-1-59745-336-3_12 · Cited by 5
A Biophysical Toolkit for Molecular Interactions
Santiveri, C. M., Mendez, B. L., Huecas, S., Alfonso, C., Luque-Ortega, J. R., & Campos‐Olivas, R. (2017) · Wiley eBooks · doi:10.1002/9780470015902.a0027015 · Cited by 5
Methods for Studying Microtubule Binding Site Interactions
Field, J. J., Calvo, E., Northcote, P. T., Miller, J. H., Altmann, K., & Díaz, J. F. (2013) · Methods in cell biology · doi:10.1016/b978-0-12-407757-7.00019-0 · Cited by 4
Self-citationChaaban, I., Khawass, E. S. M. E., Razik, H. A. A. E., Salamouni, N. S. E., Redondo‐Horcajo, M., Barasoaı́n, I., Díaz, J. F., Yli‐Kauhaluoma, J. T., & Moreira, V. M. (2016) · Archiv der Pharmazie · doi:10.1002/ardp.201600134 · Cited by 4
Self-citationEnantioselective Total Synthesis of (-)-FR182877
Suzuki, N. T., Suzuki, T., Matsumura, T., Hosoya, Y., Nakazato, T., & Nakada, M. (2011) · Journal of Synthetic Organic Chemistry Japan · doi:10.5059/yukigoseikyokaishi.69.646 · Cited by 4
Withaferin A (WIT) Interaction with beta–Tubulin to Promote Tubulin Degradation: In Silico Study
Nabati, M., Pournamdari, E., Dashti-Rahmatabadi, Y., & Sarshar, S. (2020) · Advanced Journal of Chemistry Section B · doi:10.33945/sami/ajcb.2020.1.5 · Cited by 4
Tau-isoform dependent enhancement of taxol mobility through microtubules
Park, H., Kim, M.-W., & Fygenson, D. K. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.07.020 · Cited by 4
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Canfield, P. J., Govenlock, L. J., Reimers, J. R., & Crossley, M. J. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12488525.v1 · Cited by 4
París-Ogáyar, R., Lucena‐Agell, D., Altmann, K., Palomo, V., & Díaz, J. F. (2026) · RSC Chemical Biology · doi:10.1039/d5cb00321k · Cited by 3
Self-citationPlanejamento de ligantes da tubulina com propriedades antitumorais
Salum, L. D. B. (2011) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.76.2011.tde-06122011-112559 · Cited by 3
Electrical oscillations in microtubules
Mohsin, M., Cantiello, H. F., Cantero, M. D. R., & Marucho, M. (2025) · Scientific Reports · doi:10.1038/s41598-025-24920-w · Cited by 2
Rane, D., Shaik, A. B., Lee, S., Hu, X., & Peterson, B. R. (2024) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.4c00085 · Cited by 2
Thermodynamics as a Tool for the Optimization of Drug Binding
Matesanz, R., Pera, B., & Fernando, J. (2011) · InTech eBooks · doi:10.5772/23036 · Cited by 2
Self-citationBallatore, C., Smith, A. B., Lee, V. M.-Y., Trojanowski, J. Q., & Brunden, K. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802173-6.00011-3 · Cited by 2
St.George, M. C. (2013) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r33n20p02 · Cited by 2
Kita, K., Thakkar, P. V., Galletti, G., Madhukar, N. S., Vila-Navarro, E., Barasoaı́n, I., Goodson, H. V., Sackett, D. L., Díaz, J. F., Elemento, O., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/838334 · Cited by 2
Self-citationSynthesis and Early Assessment of Epothilone‐Derived Fluorescent Probes for Microtubule Imaging
Glauser, S., París-Ogáyar, R., Lucena‐Agell, D., Palomo, V., Díaz, J. F., & Altmann, K. (2026) · ChemMedChem · doi:10.1002/cmdc.202500947 · Cited by 1
Self-citationMechanisms and kinetics of microtubule perturbing agents
Raccor, B. S. (2008) · Cited by 1
Blood pressure simulation model: a teaching aid.
Deepak, K. K. (1992) · PubMed · Cited by 1
Resistance to microtubule-stabilising agents following point mutation of human βI-tubulin
Rowe, M. R. (2015) · doi:10.26686/wgtn.17011898 · Cited by 1
Chloroacetylation of cyclostreptin influences its interaction with tubulin
Calvo, E., Barasoaı́n, I., Camafeita, E., Andreu, J. M., López, J. A., & Díaz, J. F. (2009) · DIGITAL.CSIC (Spanish National Research Council (CSIC))
Self-citationUnderstanding molecular and cellular processes using statistical physics
Wu, Z. (2011) · VTechWorks (Virginia Tech)
Enantioselective Total Synthesis of the Antitumor Polycyclic Natural Products FR182877 and Taxol
Nakada, M. (2019) · Springer eBooks · doi:10.1007/978-981-13-6244-6_3
Characterisation of Zampanolide as a Microtubule-Stabilizing Agent
Field, J. J. (2013) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.17142671.v1
Recent Advances in Stereochemistry Reveal Classification ShortcomingsPreprint
Canfield, P. J., Govenlock, L. J., Reimers, J. R., & Crossley, M. J. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12488525
Caractérisation du système microtubulaire par analyse top-down et protéomique d'affinité
Calligaris, D. (2011) · theses.fr (ABES) · doi:10.70675/b01c0bc4zcec4z4ba5z8313z533703831e2d
Talmey, Y. F. (2014) · theses.fr (ABES) · doi:10.70675/19614ee5zadd0z4838z930cz4ac6a7f7afc4
BindingDB (2017) · UC San Diego · doi:10.7270/q22n5444
Metadata
- Authors
- Buey, R. M., Calvo, E., Barasoain, I., Pineda, O., Edler, M. C., Matesanz, R., Cerezo, G., Vanderwal, C. D., Day, B. W., Sorensen, E. J., López, J. A., Andreu, J. M., Hamel, E., & Díaz, J. F.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Spanish National Centre for Cardiovascular Research (ES)
- Universitat de Barcelona (ES)
- National Institutes of Health (US)
- PharmaMar (Spain) (ES)
- University of California, Irvine (US)
- University of Pittsburgh (US)
- Princeton University (US)
- Corresponding author
- Díaz, J Fernando
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2007-01-07
- Volume
- 3
- Issue
- 2
- Pages
- 117-125
- ISSN
- 1552-4450 (ISSN-L)
- OpenAlex
- W1968782838
- Cited by
- 156
- References
- 31
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 14 · 2016: 5 · 2015: 9 · 2014: 12 · 2013: 11 · 2012: 10
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- 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 › Heterocyclic Compound Synthesis and Bioactivity
- Keywords
- microtubule stabilization, beta-tubulin, covalent binding, cell cycle arrest, tubulin assembly
- MeSH terms
- Docetaxel, Alkanes, Amino Acid Sequence, Asparagine, Binding Sites, Binding, Competitive, Carbamates, Cell Cycle, Humans, Lactones, Microtubules, Models, Chemical, Models, Molecular, Molecular Sequence Data, Polycyclic Compounds, Protein Binding, Pyrones, Mass Spectrometry, Threonine, Tubulin, Paclitaxel, Inhibitory Concentration 50, Epothilones, Taxoids, Cell Line, Tumor, Cell Proliferation, Tubulin Modulators
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