[SCAN] Exploring O2 diffusion in A-type Cytochrome c Oxidases: Insights from MD simulations

Scan Seminar

Title: Exploring O2 diffusion in A-type Cytochrome c Oxidases: Insights from MD simulations

Speaker: Ana Sofia Oliveira

From: Protein Modelling Laboratory, ITQB

Abstract

Cytochrome c oxidases (CCOX) are members of the heme-copper oxidase superfamily and are the terminal enzymes of the respiratory chain. These proteins are membrane-bound multi-subunit redox-driven proton pumps, which couple the reduction of molecular dioxygen to water with the creation of a transmembrane electrochemical proton gradient.
Over the last 20 years, most of the CCOX research focused on the mechanisms and energetics of reduction and/or proton pumping and little emphasis has been given to the pathways used by dioxygen to reach the binuclear site (BNC). The main objective of this work is to identify possible dioxygen pathways in the reduced CCOX from Rhodobacter sphaeroides [1] using extensive Molecular Dynamics (MD) simulations.
Our simulations allowed the identification of three possible dioxygen channels, all starting in the membrane hydrophobic region and connecting the surface of the protein to the BNC. One of these channels corresponds to the pathway inferred from the X-ray data available [2], whereas the other two are alternative routes for O2 to reach the BNC. Both alternative channels start in the membrane spanning region and terminate close to Y288I (which is covalently linked to the H284I imidazole group).

[1]Qin et al. (2009) Biochemistry 48, 5121-5130
[2]Svensson-EK et al. (2002) J.Mol.Biol.321, 329-339