The alkaline transition of cytochrome c revisited: Effects of electrostatic interactions and tyrosine nitration on the reaction dynamics

Archives of Biochemistry and Biophysics
Santiago Oviedo-RoucoDaniel H Murgida

Abstract

Here we investigated the effect of electrostatic interactions and of protein tyrosine nitration of mammalian cytochrome c on the dynamics of the so-called alkaline transition, a pH- and redox-triggered conformational change that implies replacement of the axial ligand Met80 by a Lys residue. Using a combination of electrochemical, time-resolved SERR spectroelectrochemical experiments and molecular dynamics simulations we showed that in all cases the reaction can be described in terms of a two steps minimal reaction mechanism consisting of deprotonation of a triggering group followed by ligand exchange. The pKaalk values of the transition are strongly modulated by these perturbations, with a drastic downshift upon nitration and an important upshift upon establishing electrostatic interactions with a negatively charged model surface. The value of pKaalk is determined by the interplay between the acidity of a triggering group and the kinetic constants for the forward and backward ligand exchange processes. Nitration of Tyr74 results in a change of the triggering group from Lys73 in WT Cyt to Tyr74 in the nitrated protein, which dominates the pKaalk downshift towards physiological values. Electrostatic interactions, on the other ha...Continue Reading

Citations

Jan 23, 2021·The Biochemical Journal·Matthias FellnerElizabeth C Ledgerwood
Mar 12, 2021·Biochemistry. Biokhimii︠a︡·Erik SedlákNataša Tomášková
Jun 23, 2020·Inorganic Chemistry·Inmaculada MárquezJuan José Calvente
Jan 4, 2020·Archives of Biochemistry and Biophysics·Santiago Oviedo-RoucoDaniel H Murgida

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