Jump to main content
Jump to site search

Issue 9, 2015
Previous Article Next Article

Fluorine teams up with water to restore inhibitor activity to mutant BPTI

Author affiliations

Abstract

Introducing fluorine into molecules has a wide range of effects on their physicochemical properties, often desirable but in most cases unpredictable. The fluorine atom imparts the C–F bond with low polarizability and high polarity, and significantly affects the behavior of neighboring functional groups, in a covalent or noncovalent manner. Here, we report that fluorine, present in the form of a single fluoroalkyl amino acid side chain in the P1 position of the well-characterized serine-protease inhibitor BPTI, can fully restore inhibitor activity to a mutant that contains the corresponding hydrocarbon side chain at the same site. High resolution crystal structures were obtained for four BPTI variants in complex with bovine β-trypsin, revealing changes in the stoichiometry and dynamics of water molecules in the S1 subsite. These results demonstrate that the introduction of fluorine into a protein environment can result in “chemical complementation” that has a significantly favorable impact on protein–protein interactions.

Graphical abstract: Fluorine teams up with water to restore inhibitor activity to mutant BPTI

Back to tab navigation

Supplementary files

Publication details

The article was received on 21 Oct 2014, accepted on 11 Jun 2015 and first published on 12 Jun 2015


Article type: Edge Article
DOI: 10.1039/C4SC03227F
Citation: Chem. Sci., 2015,6, 5246-5254
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Fluorine teams up with water to restore inhibitor activity to mutant BPTI

    S. Ye, B. Loll, A. A. Berger, U. Mülow, C. Alings, M. C. Wahl and B. Koksch, Chem. Sci., 2015, 6, 5246
    DOI: 10.1039/C4SC03227F

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements