IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36481-5.html
   My bibliography  Save this article

Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography

Author

Listed:
  • Maximilian Wranik

    (Paul Scherrer Institut)

  • Tobias Weinert

    (Paul Scherrer Institut)

  • Chavdar Slavov

    (Goethe University)

  • Tiziana Masini

    (Istituto Italiano di Tecnologia)

  • Antonia Furrer

    (Paul Scherrer Institut)

  • Natacha Gaillard

    (Paul Scherrer Institut)

  • Dario Gioia

    (Istituto Italiano di Tecnologia)

  • Marco Ferrarotti

    (Istituto Italiano di Tecnologia)

  • Daniel James

    (Paul Scherrer Institut)

  • Hannah Glover

    (Paul Scherrer Institut)

  • Melissa Carrillo

    (Paul Scherrer Institut)

  • Demet Kekilli

    (Paul Scherrer Institut)

  • Robin Stipp

    (Paul Scherrer Institut)

  • Petr Skopintsev

    (Paul Scherrer Institut)

  • Steffen Brünle

    (Paul Scherrer Institut)

  • Tobias Mühlethaler

    (Paul Scherrer Institut)

  • John Beale

    (Paul Scherrer Institut)

  • Dardan Gashi

    (Paul Scherrer Institut)

  • Karol Nass

    (Paul Scherrer Institut)

  • Dmitry Ozerov

    (Paul Scherrer Institut)

  • Philip J. M. Johnson

    (Paul Scherrer Institut)

  • Claudio Cirelli

    (Paul Scherrer Institut)

  • Camila Bacellar

    (Paul Scherrer Institut)

  • Markus Braun

    (Goethe University)

  • Meitian Wang

    (Paul Scherrer Institut)

  • Florian Dworkowski

    (Paul Scherrer Institut)

  • Chris Milne

    (Paul Scherrer Institut)

  • Andrea Cavalli

    (Istituto Italiano di Tecnologia
    University of Bologna)

  • Josef Wachtveitl

    (Goethe University)

  • Michel O. Steinmetz

    (Paul Scherrer Institut
    University of Basel)

  • Jörg Standfuss

    (Paul Scherrer Institut)

Abstract

The binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology. Using time-resolved serial crystallography at a synchrotron and X-ray free-electron laser, we capture the release of the anti-cancer compound azo-combretastatin A4 and the resulting conformational changes in tubulin. Nine structural snapshots from 1 ns to 100 ms complemented by simulations show how cis-to-trans isomerization of the azobenzene bond leads to a switch in ligand affinity, opening of an exit channel, and collapse of the binding pocket upon ligand release. The resulting global backbone rearrangements are related to the action mechanism of microtubule-destabilizing drugs.

Suggested Citation

  • Maximilian Wranik & Tobias Weinert & Chavdar Slavov & Tiziana Masini & Antonia Furrer & Natacha Gaillard & Dario Gioia & Marco Ferrarotti & Daniel James & Hannah Glover & Melissa Carrillo & Demet Keki, 2023. "Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36481-5
    DOI: 10.1038/s41467-023-36481-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36481-5
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-36481-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Agata Butryn & Philipp S. Simon & Pierre Aller & Philip Hinchliffe & Ramzi N. Massad & Gabriel Leen & Catherine L. Tooke & Isabel Bogacz & In-Sik Kim & Asmit Bhowmick & Aaron S. Brewster & Nicholas E., 2021. "An on-demand, drop-on-drop method for studying enzyme catalysis by serial crystallography," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    2. Petr Skopintsev & David Ehrenberg & Tobias Weinert & Daniel James & Rajiv K. Kar & Philip J. M. Johnson & Dmitry Ozerov & Antonia Furrer & Isabelle Martiel & Florian Dworkowski & Karol Nass & Gregor K, 2020. "Femtosecond-to-millisecond structural changes in a light-driven sodium pump," Nature, Nature, vol. 583(7815), pages 314-318, July.
    3. Tobias Weinert & Natacha Olieric & Robert Cheng & Steffen Brünle & Daniel James & Dmitry Ozerov & Dardan Gashi & Laura Vera & May Marsh & Kathrin Jaeger & Florian Dworkowski & Ezequiel Panepucci & Shi, 2017. "Serial millisecond crystallography for routine room-temperature structure determination at synchrotrons," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    4. Uwe Weierstall & Daniel James & Chong Wang & Thomas A. White & Dingjie Wang & Wei Liu & John C. H. Spence & R. Bruce Doak & Garrett Nelson & Petra Fromme & Raimund Fromme & Ingo Grotjohann & Christoph, 2014. "Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography," Nature Communications, Nature, vol. 5(1), pages 1-6, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Maximilian Wranik & Michal W. Kepa & Emma V. Beale & Daniel James & Quentin Bertrand & Tobias Weinert & Antonia Furrer & Hannah Glover & Dardan Gashi & Melissa Carrillo & Yasushi Kondo & Robin T. Stip, 2023. "A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Maximilian Wranik & Michal W. Kepa & Emma V. Beale & Daniel James & Quentin Bertrand & Tobias Weinert & Antonia Furrer & Hannah Glover & Dardan Gashi & Melissa Carrillo & Yasushi Kondo & Robin T. Stip, 2023. "A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Basudev Maity & Mitsuo Shoji & Fangjia Luo & Takanori Nakane & Satoshi Abe & Shigeki Owada & Jungmin Kang & Kensuke Tono & Rie Tanaka & Thuc Toan Pham & Mariko Kojima & Yuki Hishikawa & Junko Tanaka &, 2024. "Real-time observation of a metal complex-driven reaction intermediate using a porous protein crystal and serial femtosecond crystallography," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Kaihua Zhang & Hao Wu & Nicholas Hoppe & Aashish Manglik & Yifan Cheng, 2022. "Fusion protein strategies for cryo-EM study of G protein-coupled receptors," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Elizaveta Lyapina & Egor Marin & Anastasiia Gusach & Philipp Orekhov & Andrey Gerasimov & Aleksandra Luginina & Daniil Vakhrameev & Margarita Ergasheva & Margarita Kovaleva & Georgii Khusainov & Polin, 2022. "Structural basis for receptor selectivity and inverse agonism in S1P5 receptors," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Michael W. Martynowycz & Anna Shiriaeva & Max T. B. Clabbers & William J. Nicolas & Sara J. Weaver & Johan Hattne & Tamir Gonen, 2023. "A robust approach for MicroED sample preparation of lipidic cubic phase embedded membrane protein crystals," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Susannah Holmes & Henry J. Kirkwood & Richard Bean & Klaus Giewekemeyer & Andrew V. Martin & Marjan Hadian-Jazi & Max O. Wiedorn & Dominik Oberthür & Hugh Marman & Luigi Adriano & Nasser Al-Qudami & S, 2022. "Megahertz pulse trains enable multi-hit serial femtosecond crystallography experiments at X-ray free electron lasers," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. E. Podoliak & G. H. U. Lamm & E. Marin & A. V. Schellbach & D. A. Fedotov & A. Stetsenko & M. Asido & N. Maliar & G. Bourenkov & T. Balandin & C. Baeken & R. Astashkin & T. R. Schneider & A. Bateman &, 2024. "A subgroup of light-driven sodium pumps with an additional Schiff base counterion," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. M. Wilamowski & D. A. Sherrell & Y. Kim & A. Lavens & R. W. Henning & K. Lazarski & A. Shigemoto & M. Endres & N. Maltseva & G. Babnigg & S. C. Burdette & V. Srajer & A. Joachimiak, 2022. "Time-resolved β-lactam cleavage by L1 metallo-β-lactamase," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36481-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.