Molecular dynamics simulations of carbon monoxide dissociation from heme a3 in cytochrome c oxidase from Paracoccus denitrificans

We have investigated ligand motions in the heme a(3)-CuB binuclear active site of cytochrome c oxidase by molecular dynamics simulations. The starting structural model is based on the two-subunit structure from the Paracoccus denitrificans enzyme and contains carbon monoxide (CO) bound to heme a(3). Short (1 ps) trajectories of the enzyme were calculated, each initiated by the sudden breaking of the Fea(3)-CO bond. A comparison of two sets of calculations suggests a functional mechanistic role of the covalent bond between Tyr280 and His276, the latter being one of the three histidines coordinating the copper atom CuB. In particular, the presence of this bond enhances the coupling of the CO motion to the environment and confines motion of CO on the picosecond time scale to the region close to CuB. On the time scale of a few hundred femtoseconds after dissociation, the most important movement of CO consists of rotation over similar to 90 degrees and the most favorable position for binding to CuB appears to be occupied after 300-400 fs. These results are discussed in the light of the recent suggestion that the reaction coordinate of coherent reaction dynamics of heme a(3) after photodissociation involves CO transfer to CuB (Liebl, U.; Lipowski, G.; Negrerie, M.; Lambry J.-C.; Martin, J.-L.; Vos, M. H. Nature 1999, 401, 181.).