Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 13, 2020
Previous Article Next Article

Thermodynamic consequences of Tyr to Trp mutations in the cation–π-mediated binding of trimethyllysine by the HP1 chromodomain

Author affiliations

Abstract

Evolution has converged on cation–π interactions for recognition of quaternary alkyl ammonium groups such as trimethyllysine (Kme3). While computational modelling indicates that Trp provides the strongest cation–π interaction of the native aromatic amino acids, there is limited corroborative data from measurements within proteins. Herein we investigate a Tyr to Trp mutation in the binding pocket of the HP1 chromodomain, a reader protein that recognizes Kme3. Binding studies demonstrate that the Trp-mediated cation–π interaction is about −5 kcal mol−1 stronger, and the Y24W crystal structure shows that the mutation is not perturbing. Quantum mechanical calculations indicate that greater enthalpic binding is predominantly due to increased cation–π interactions. NMR studies indicate that differences in the unbound state of the Y24W mutation lead to enthalpy–entropy compensation. These results provide direct experimental quantification of Trp versus Tyr in a cation–π interaction and afford insight into the conservation of aromatic cage residues in Kme3 reader domains.

Graphical abstract: Thermodynamic consequences of Tyr to Trp mutations in the cation–π-mediated binding of trimethyllysine by the HP1 chromodomain

Back to tab navigation

Supplementary files

Article information


Submitted
13 Jan 2020
Accepted
03 Mar 2020
First published
04 Mar 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 3495-3500
Article type
Edge Article

Thermodynamic consequences of Tyr to Trp mutations in the cation–π-mediated binding of trimethyllysine by the HP1 chromodomain

M. W. Krone, K. I. Albanese, G. O. Leighton, C. Q. He, G. Y. Lee, M. Garcia-Borràs, A. J. Guseman, D. C. Williams, K. N. Houk, E. M. Brustad and M. L. Waters, Chem. Sci., 2020, 11, 3495
DOI: 10.1039/D0SC00227E

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.


Social activity

Search articles by author

Spotlight

Advertisements