J Biol Chem, Vol. 273, Issue 5, 2501-2504, January 30, 1998

COMMUNICATION
Modeling Charge Interactions and Redox Properties in DsbA

From the Institute of Food Research, Reading Laboratory, Earley Gate, Whiteknights Road, Reading RG6 6BZ, United Kingdom

Accurate prediction of charge interactions in macromolecules presents a significant challenge for computational biology. A model for the low Cys³⁰ pK_a 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 pK_a 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 pK_a.