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Theoretical investigation of the behavior of titratable groups in proteins

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Abstract

This paper presents a theoretical analysis of the titration behavior of strongly interacting titratable residues in proteins. Strongly interacting titratable residues exist in many proteins such as for instance bacteriorhodopsin, cytochrome c oxidase, cytochrome bc1, or the photosynthetic reaction center. Strong interaction between titratable groups can lead to irregular titration behavior. We analyze under which circumstances titration curves can become irregular. We demonstrate that conformational flexibility alone can not lead to irregular titration behavior. Strong interaction between titratable groups is a necessary, but not sufficient condition for irregular titration curves. In addition, the two interacting groups also need to titrate in the same pH-range. These two conditions together lead to irregular titration curves. The mutation of a single residue within a cluster of interacting titratable residues can influence the titration behavior of the other titratable residues in the cluster. We demonstrate this effect on a cluster of four interacting residues. This example underlines that mutational studies directed at identifying the role of a certain titratable residue in a cluster of interacting residues should always be accompanied by an analysis of the effect of the mutation on the titration behavior of the other residues.

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Authors and Affiliations

  1. Structural Biology/Bioinformatics, University of Bayreuth, Universitätsstr. 30 BGI, D-95447 Bayreuth, Germany

    Astrid R. Klingen, Elisa Bombarda & G. Matthias Ullmann

  2. Département Pharmacochimie de la Communication Cellulaire-UMR 7175-LC1, Université Louis Pasteur, 74 route du Rhin, F-67401, Illkirch Cedex, France

    Elisa Bombarda

Authors
  1. Astrid R. Klingen
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  2. Elisa Bombarda
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  3. G. Matthias Ullmann
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Correspondence to G. Matthias Ullmann.

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† This paper was published as part of the special issue on Proton Transfer in Biological Systems.

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Klingen, A.R., Bombarda, E. & Ullmann, G.M. Theoretical investigation of the behavior of titratable groups in proteins. Photochem Photobiol Sci 5, 588–596 (2006). https://doi.org/10.1039/b515479k

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