IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38339-2.html
   My bibliography  Save this article

Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer

Author

Listed:
  • David P. Tilly

    (University of Bristol, Cantock’s Close
    University of Manchester)

  • Jean-Paul Heeb

    (University of Bristol, Cantock’s Close)

  • Simon J. Webb

    (University of Manchester)

  • Jonathan Clayden

    (University of Bristol, Cantock’s Close)

Abstract

Molecular biology achieves control over complex reaction networks by means of molecular systems that translate a chemical input (such as ligand binding) into an orthogonal chemical output (such as acylation or phosphorylation). We present an artificial molecular translation device that converts a chemical input – the presence of chloride ions – into an unrelated chemical output: modulation of the reactivity of an imidazole moiety, both as a Brønsted base and as a nucleophile. The modulation of reactivity operates through the allosteric remote control of imidazole tautomer states. The reversible coordination of chloride to a urea binding site triggers a cascade of conformational changes in a chain of ethylene-bridged hydrogen-bonded ureas, switching the chain’s global polarity, that in turn modulates the tautomeric equilibrium of a distal imidazole, and hence its reactivity. Switching reactivities of active sites by dynamically controlling their tautomer states is an untapped strategy for building functional molecular devices with allosteric enzyme-like properties.

Suggested Citation

  • David P. Tilly & Jean-Paul Heeb & Simon J. Webb & Jonathan Clayden, 2023. "Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38339-2
    DOI: 10.1038/s41467-023-38339-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38339-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38339-2?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. Hesam N. Motlagh & James O. Wrabl & Jing Li & Vincent J. Hilser, 2014. "The ensemble nature of allostery," Nature, Nature, vol. 508(7496), pages 331-339, April.
    Full references (including those not matched with items on IDEAS)

    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. Zhihong Xiao & Jinyin Zha & Xu Yang & Tingting Huang & Shuxin Huang & Qi Liu & Xiaozheng Wang & Jie Zhong & Jianting Zheng & Rubing Liang & Zixin Deng & Jian Zhang & Shuangjun Lin & Shaobo Dai, 2024. "A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Zhong Guo & Oleh Smutok & Wayne A. Johnston & Patricia Walden & Jacobus P. J. Ungerer & Thomas S. Peat & Janet Newman & Jake Parker & Tom Nebl & Caryn Hepburn & Artem Melman & Richard J. Suderman & Ev, 2021. "Design of a methotrexate-controlled chemical dimerization system and its use in bio-electronic devices," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Yuya Nishida & Sachiko Yanagisawa & Rikuri Morita & Hideki Shigematsu & Kyoko Shinzawa-Itoh & Hitomi Yuki & Satoshi Ogasawara & Ken Shimuta & Takashi Iwamoto & Chisa Nakabayashi & Waka Matsumura & His, 2022. "Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Manuel Weh & Kazutaka Shoyama & Frank Würthner, 2023. "Preferential molecular recognition of heterochiral guests within a cyclophane receptor," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    5. Federica Maschietto & Uriel N. Morzan & Florentina Tofoleanu & Aria Gheeraert & Apala Chaudhuri & Gregory W. Kyro & Peter Nekrasov & Bernard Brooks & J. Patrick Loria & Ivan Rivalta & Victor S. Batist, 2023. "Turning up the heat mimics allosteric signaling in imidazole-glycerol phosphate synthase," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Marko Novinec, 2017. "Computational investigation of conformational variability and allostery in cathepsin K and other related peptidases," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-22, August.
    7. Zhong Guo & Rinky D. Parakra & Ying Xiong & Wayne A. Johnston & Patricia Walden & Selvakumar Edwardraja & Shayli Varasteh Moradi & Jacobus P. J. Ungerer & Hui-wang Ai & Jonathan J. Phillips & Kirill A, 2022. "Engineering and exploiting synthetic allostery of NanoLuc luciferase," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. Leonila Lagunes & Lee Bardwell & German A Enciso, 2020. "Effect of magnitude and variability of energy of activation in multisite ultrasensitive biochemical processes," PLOS Computational Biology, Public Library of Science, vol. 16(8), pages 1-26, August.
    9. Yichen Yu & Robert T. O’Neill & Roman Boulatov & Ross A. Widenhoefer & Stephen L. Craig, 2023. "Allosteric control of olefin isomerization kinetics via remote metal binding and its mechanochemical analysis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    10. Robert Kalescky & Hongyu Zhou & Jin Liu & Peng Tao, 2016. "Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery," PLOS Computational Biology, Public Library of Science, vol. 12(4), pages 1-21, April.
    11. Jonathan Schubert & Andrea Schulze & Chrisostomos Prodromou & Hannes Neuweiler, 2021. "Two-colour single-molecule photoinduced electron transfer fluorescence imaging microscopy of chaperone dynamics," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    12. Luhao Zhang & Maodong Li & Zhirong Liu, 2018. "A comprehensive ensemble model for comparing the allosteric effect of ordered and disordered proteins," PLOS Computational Biology, Public Library of Science, vol. 14(12), pages 1-22, 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_s41467-023-38339-2. 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.