Living with Oxygen.

Area of Science:

• Biochemistry and Inorganic Chemistry
• Enzyme mechanisms and metallo-organic chemistry

Background:

• Early work predicted stability limits for metal-oxo complexes, but high-valent iron-oxos are now recognized as crucial biological intermediates.
• Cytochromes P450 utilize high-valent iron-oxos for oxygenating inert substrates, posing a reactivity challenge due to their potent oxidizing nature.

Purpose of the Study:

• To investigate the protective mechanisms employed by enzymes, particularly cytochromes P450, against highly reactive high-valent iron-oxo species.
• To elucidate the role of amino acid residues, specifically tyrosine and tryptophan, in managing the reactivity of these dangerous oxygen species.

Main Methods:

• Analysis of numerous protein structures from the Protein Data Bank to identify conserved amino acid patterns near active sites.
• Examination of hole hopping mechanisms and survival times of high-valent iron-oxos, correlated with the proximity of tyrosine and tryptophan residues.

Main Results:

• Enzymes like P450 possess tyrosine and tryptophan chains extending from active sites to protein surfaces.
• The distance of these residues influences the survival time of high-valent iron-oxos, with shorter distances correlating to faster quenching.
• A proposed mechanism involves multistep hole tunneling through these amino acid chains to safely quench oxidants on the protein surface.

Conclusions:

• Tyrosine and tryptophan residues act as protective conduits, channeling damaging oxidizing holes away from the active site to prevent self-destruction.
• The evolution of these protective pathways may be linked to the rise of an oxygenic atmosphere, necessitating defense against reactive oxygen species.