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Pure Appl. Chem., 2004, Vol. 76, No. 2, pp. 303-319

Understanding the reaction that powers this world: Biomimetic studies of respiratory O2 reduction by cytochrome oxidase*

R. Boulatov

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA

Abstract: Cytochrome c oxidase (CcO) is an enzyme that catalyzes efficient, selective, and fast reduction of molecular oxygen to water as a means of respiratory energy generation. The biomimetic approach provides a valuable alternative to traditional biochemical methods to unravel the structural and electronic properties of the CcO's catalytic (heme/CuB) site that endow the enzyme with its unique reactivity. However, the contribution of biomimetic studies of CcO to our understanding of CcO's biochemistry has been complicated by the lack of convincing evidence that the reactivity of the biomimetic analogs is relevant to that of CcO. Recently reported porphyrin-based compounds are the first analogs that reproduce key aspects of the reactivity of CcO toward O2. Extensive data collected with these biomimetic analogs demonstrate that the bimetallic nature of the CcO's catalytic site may be an adaptation to reduction of O2 under turnover-limiting electron flux; a monometallic heme-only site appears sufficient for rapid O2 reduction under physiologically relevant conditions of pH and electrochemical potential, provided that electron flow to the heme is not kinetically limited. These biomimetic data suggest that in CcO the distal Cu ion (CuB) may serve as an electron-preloading site to allow the enzyme to accumulate a sufficient number of external reducing equivalents before it even binds O2. This mechanism minimizes the population of enzymatic species containing partially reduced oxygen species.
*Pure Appl. Chem. 76, 263-319 (2004). A collection of invited, peer-reviewed articles by the winners of the 2003 IUPAC Prize for Young Chemists.

Errata to this article were published in:
Pure Appl. Chem., 2004, Vol. 76, No. 6, pp. 1293