Kinetics of the Terminal Electron Transfer Step in Cytochrome c Oxidase

Abstract

Cytochrome c oxidase (cco) catalyzes the oxygen reduction reaction in most aerobically respiring organisms. Decades of research have uncovered many aspects relating to structure and function of this enzyme. However, the origin of the unusually fast terminal electron transfer step from heme a to heme a(3) in cco has been the subject of intense discussions over recent years. Yet, no satisfactory consensus has been achieved. Carrying out large-scale molecular dynamics simulation of the protein embedded in a solvated membrane, we obtain a reorganization free energy λ = 0.57 eV. Evaluation of the quantized single-mode rate equation using the experimental rate and the computed reorganization free energy gives a value of 1.5 meV for the average electronic coupling (H(ab)) between heme a and heme a(3). Thus, according to our calculations, the nanosecond electron transfer (ET) is due to a small but significant activation barrier (ΔG(‡) = 0.12 eV) in combination with effective electronic coupling between the two cofactors. The activation free energy is caused predominantly by collective reorganization of protein residues. We show that our results are consistent with the weak temperature dependence observed in experiment if one allows for very minor variations in the donor-acceptor distance as the temperature changes.

Electron flow in multiheme bacterial cytochromes is a balancing act between heme electronic interaction and redox potentials

“…The classical MD simulations were carried out with the the AMBER03 protein force field (36) together with the TIP3P water model (37). Force field parameters for the heme cofactors were taken from earlier work (32,38,39).…”

Multi-haem cytochromes inShewanella oneidensisMR-1: structures, functions and opportunities

“…Hence, the overlap and coupling are highly sensitive on the orientation of donor and acceptor [115]. (It remains unclear also what the effective packing density should be for close cofactor contacts: for the haem pair in cytochrome c oxidase with an edge-to-edge distance of ca 7 Å , a packing density reduced by a third was suggested [105].) While the orientational aspect is not excluded in the pathway model (as the relative orientation of two cofactors determines, for example, the lengths of different through-space contacts), the latter still does not take into consideration the actual coupling orbital shapes (and treats all through-space contacts as equally important).…”

New force field parameters for metalloproteins I: Divalent copper ion centers including three histidine residues and an oxygen‐ligated amino acid residue

“…Burger et al utilized the Seminario method to determine force constants for a Zn(II) scaffold composed of bis‐dipicolylamine bound to phosphotyrosine . Additionally, Tipmanee and Blumberger calculated the bond and angle force constants for the heme a, heme a 3 , Cu A , and Cu B centers of cytochrome c oxidase . Altogether, these studies have demonstrated the usefulness of Seminario's method for deriving the force constant parameters of simple small molecule systems to larger metalloprotein coordination complexes.…”