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Published September 7, 2001 | public
Journal Article

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.

Additional Information

© 2001 American Association for the Advancement of Science. 16 May 2001; accepted 12 July 2001. We thank members of the Scripps Research Institute mass spectroscopy facility, especially G. Suizdak and M. Sonderegger, for assistance with the isotope analysis; L. Teyton for the 2C TCRab; M. Pique for Kabat database analysis; K. Quon for ICP-AES antibody analyses; B. Zhou for mutagenesis studies; P. G. Schultz for helpful discussions; D. Datta, N. Vaidehi, R. P. Muller, and D. Chakraborty for stimulating discussions; and several Wilson lab members for help with data collection and processing, especially X. Daio. Supported by NIH grants GM43858 (K.D.J.), CA27489 (program project grant; K.D.J., I.A.W., R.A.L.), and HD 36385 (W.A.G.).

Additional details

Created:
August 19, 2023
Modified:
October 18, 2023