title: Modeling charge interactions and redox properties in DsbA.
abstract: Accurate prediction of charge interactions in macromolecules presents a significant challenge for computational biology. A model for the low Cys30 pKa and oxidizing power of DsbA (Gane, P. J., Freedman, R. B., and Warwicker, J. (1995) J. Mol. Biol. 249, 376-387) has been investigated experimentally (Hennecke, J., Spleiss, C., and Glockshuber, R. (1997) J. Biol. Chem. 272, 189-195), with substitutions for Glu37 and Glu38 and with residues 38-40 removed. Measured changes in Cys30 pKa and redox potential were relatively small and reported to be in contrast to model predictions. It is now shown, particularly with calculations of wild-type:mutant differences for a range of salt concentrations, that the data are consistent with the model and support the key finding that a number of different factors contribute to the oxidizing power of DsbA, so that any particular one need not necessarily be large. A feature of the model is a low protein dielectric, and higher values (which are becoming popular in predictions of pH dependence) are inconsistent with both the difference data and the wild-type Cys30 pKa.
authors.affiliation: Institute of Food Research, Reading Laboratory, Earley Gate, Whiteknights Road, Reading RG6 6BZ, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Warwicker
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli; D007477:Ions; D008956:Models, Chemical; D009154:Mutation; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000235:genetics; D055672:Static Electricity
chemical_list: D001426:Bacterial Proteins; D007477:Ions; D019704:Protein Disulfide-Isomerases