Antibody Catalysis of the Oxidation of Water

Abstract

Recently we reported that antibodies can generate hydrogen peroxide (H_2O_2) from singlet molecular oxygen (^1O_2^*). We now show that this process is catalytic, and we identify the electron source for a quasi-unlimited generation of H_2O_2. Antibodies produce up to 500 mole equivalents of H_2O_2 from^1O_2^*, without a reduction in rate, and we have excluded metals or Cl– as the electron source. On the basis of isotope incorporation experiments and kinetic data, we propose that antibodies use H_2O as an electron source, facilitating its addition to ^1O_2^* to form H_2O_3 as the first intermediate in a reaction cascade that eventually leads to H_2O_2. X-ray crystallographic studies with xenon point to putative conserved oxygen binding sites within the antibody fold where this chemistry could be initiated. Our findings suggest a protective function of immunoglobulins against ^1O_2^* and raise the question of whether the need to detoxify ^1O_2^* has played a decisive role in the evolution of the immunoglobulin fold.

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