METAL-METAL BONDING IN BIOLOGY - EXAFS EVIDENCE FOR A 2.5-ANGSTROM COPPER-COPPER BOND IN THE CU-A CENTER OF CYTOCHROME-OXIDASE

Evidence for a direct Cu-Cu bond in the Cu-A center of cytochrome oxidase is reported. Simulation of the X-ray absorption spectrum of a recombinant Cu-A-binding domain of Bacillus subtilis cytochrome oxidase, and comparison with a structurally characterized directly-bonding Cu(1.5)...Cu(1.5) inorganic complex, suggests that a Cu-Cu interaction of 2.5 +/- 0.1 Angstrom together with a short 2.2 Angstrom Cu-S interaction may be present in the Cu-A site. In light of these data, previous interpretations of the EXAFS of a number of cytochrome oxidase and nitrous oxide reductase enzymes which modeled the 2.6 Angstrom interaction as a long Cu-S(methionine) bona are possibly incorrect. A structural model based on the new data is presented which suggests that the Cu-A sites in cytochrome oxidase and N2O reductase are likely composed of a pair of modified type 1 copper centers with one histidine, one cysteine, and one weakly bound ligand (Met and/or Gln) joined by a Cu-Cu bond.