STRUCTURE AND DYNAMICS OF A PROTON SHUTTLE IN CYTOCHROME-C-OXIDASE

Protein-assisted transport of protons across the bioenergetic membrane is mediated by hydrogen-bonded networks. These networks involve titra table amino acid residues of membrane-spanning protein assemblies as w ell as internal water molecules. In cytochrome c oxidase, the so-calle d D-channel defines such a network for the uptake of protons from the cytoplasmic side of the membrane. It has been proposed that conformati onal changes of a Glu residue are required for the establishment of a proton linkage from the channel into the active site. The thermodynami c basis for the conformational isomerization of this residue is invest igated using simulated annealing and free energy molecular dynamics si mulations. The results support the existence of metastable conformatio ns of the side chain, and their interchange through local structural f luctuations of neighboring residues and nearby internal chains of wate r molecules. The conformational isomerization of both protonated and u nprotonated states of Glu, coupled with the reorganization of hydrogen bonds, suggests a kinetically competent mechanism for proton shuttlin g. (C) 1998 Elsevier Science BN.