title: Theoretical investigation of the behavior of titratable groups in proteins.
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 bc(1), 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.
authors.affiliation: Structural Biology/Bioinformatics, University of Bayreuth, Universitätsstrasse 30, BGI, D-95447 Bayreuth, Germany.
authors.forename: Astrid R
authors.initials: AR
authors.lastname: Klingen
authors.forename: Elisa
authors.initials: E
authors.lastname: Bombarda
authors.forename: G Matthias
authors.initials: GM
authors.lastname: Ullmann
mesh_terms: D006863:Hydrogen-Ion Concentration; D009154:Mutation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics
chemical_list: D011506:Proteins