STSRUCTURE, FUNCTION AND STRUCTURAL ORGANIZATION OF MITOCHONDRIAL CYTOCHROME c OXIDASE
TOMITAKE TSUKIHARA
The mitochondrial inner-membrane contains several respiratory enzyme complexes. Cytochrome c oxidase accepts electrons from cytochrome c at the inter-membrane side, and reduces a dioxygen molecule to waters coupling with pumping protons from matrix space to inter membrane space. Protons accumulated in the inter membrane space are utilized to generate ATP by ATPase. This enzyme is compared to a car engine, which uses proton and electron as fuel. A dioxigen molecule is reduced at an active center of cytochrome c oxidase. The active center functions as a cylinder of the car engine. Electrons and dioxygen molecules are supplied for the active center from the inter membrane space. Protons used as fuel are taken from the matrix space. This enzyme complex has been one of the most actively studied enzymes in the field of bioenergetics due to its physiological importance and to the intriguing nature of the catalytic mechanism.
X-ray structures for this enzyme have given rise to a new stage in cytochrome c oxidase research. We have determined the crystal and molecular structures of bovine heart cytochrome c oxidase at several states. The enzyme forms a dimer in crystalline state consisting of two copies of 13 different subunits which traverses the mitochondrial inner membrane. The transmembrane part of each monomer consists of 28 a-helices, including metal centers of heme a, heme a3 and CuB at the same level in the membrane. Another metal center of CuA is located in the inter membrane part of the enzyme complex. A pathway for electron transport from CuA to the dioxygen reduction site and a possible pathway for proton translocation, as well as a proton pumping mechanism, in the bovine heart enzyme has been proposed.
The enzyme is a typical hybrid protein complex, whose ten subunits are encoded by the nuclear DNA and the other three encoded by the mitochondrial DNA are synthesized in the matrix space of the mitochondrion. A hierarchy of structural organization of bovine cytochrome c oxidase was elucidated by inspecting quaternary structure of the enzyme complex.