Zheng, Guishan, Schaefer, Michael and Karplus, Martin (2013) Hemoglobin Bohr Effects: Analysis of the Histidine Residue Contributions. Biochemistry.

Abstract

The Bohr effect in hemoglobin, which refers to the dependence of the oxygen affinity on the pH, plays an important role in its cooperativity and physiological function. The dominant contribution to the Bohr effect arises from the difference in the pKa values of this residue of the unliganded (deoxy) and liganded (carbonmonoxy) structures. Using recent high resolution structures for the two states, the residue pKa values corresponding to the two structures are calculated with a method based on determining the electrostatic interaction with the linearized finite difference Poisson-Boltzmann equation and Monte Carlo sampling of protonation states. Good agreement with the available experimental values is observed, so that a meaningful analysis of the origin of the pKa shift between the two structures can be made. By decomposing the contributions to the pKa shift, it is shown that the salt bridge involving His146 plays an important role in the alkaline Bohr effect, as suggested by Perutz, but many other interactions are significant as well. The method used is summarized and the implemented program is described in the Appendix.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/10835