The modified Tanford-Kirkwood theory of Shire et al. [Shire, S. J., Hanania, G.I.H., & Gurd, F.R.N. (1974) Biochemistry 13, 2967] for electrostatic interactions was applied to the hydrogen ion equilibria of human deoxyhemoglobin and oxyhemoglobin. Atomic coordinates for oxyhemoglobin were generated by the application of the appropriate rigid rotation function to alpha and beta chains of the deoxyhemoglobin structure [Fermi, G. (1975) J. Mol. Biol. 97, 237]. The model employs two sets of parameters derived from the crystalline protein structures, the atomic coordinates of charged amino acid residues and static solvent accessibility factors to reflect their individual degrees of exposure to solvent. Theoretical titration curves based on a consistent set of pKint values compared closely with experimental potentiometric curves. Theoretical pK values at half-titration for individual protein sites corresponded to available observed values for both quaternary states. The results bring out the cumulative effects of numerous electrostatic interactions in the tetrameric structures and the major effects of the quaternary transition that result from changes in static solvent accessibility of certain ionizable groups.
Cytochrome c and cytochrome b5 form an electrostatically associated electron transfer complex. Computer models of this and related complexes that were generated by docking the x-ray structures of the individual proteins have provided insight into the specificity and mechanism of electron transfer reactions. Previous static modeling studies were extended by molecular dynamics simulations of a cytochrome c-cytochrome b5 intermolecular complex. The simulations indicate that electrostatic interactions at the molecular interface results in a flexible association complex that samples alternative interheme geometries and molecular conformations. Many of these transient geometries appear to be more favorable for electron transfer than those formed in the initial model complex. Of particular interest is a conformational change that occurred in phenylalanine 82 of cytochrome c that allowed the phenyl side chain to bridge the two cytochrome heme groups.
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