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Antibody catalysis of the oxidation of water

Academic Article
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Overview

related to degree

  • Larsen, Nicholas, Ph.D. in Biology, Scripps Research 1998 - 2002

authors

  • Wentworth Jr., Paul
  • Jones, L. H.
  • Wentworth, A. D.
  • Zhu, X. Y.
  • Larsen, Nicholas
  • Wilson, Ian
  • Xu, X.
  • Goddard, W. A.
  • Janda, Kim
  • Eschenmoser, A.
  • Lerner, Richard

publication date

  • September 2001

journal

  • Science  Journal

abstract

  • Recently we reported that antibodies can generate hydrogen peroxide (H2O2) from singlet molecular oxygen (1O2*). We now show that this process is catalytic, and we identify the electron source for a quasi-unlimited generation of H2O2. Antibodies produce up to 500 mole equivalents of H2O2 from 1O2*, 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 H2O as an electron source, facilitating its addition to 1O2* to form H2O3 as the first intermediate in a reaction cascade that eventually leads to H2O2. 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 1O2* and raise the question of whether the need to detoxify 1O2* has played a decisive role in the evolution of the immunoglobulin fold.

subject areas

  • Animals
  • Antibodies, Catalytic
  • Binding Sites
  • Catalysis
  • Conserved Sequence
  • Crystallography, X-Ray
  • Humans
  • Hydrogen Peroxide
  • Kinetics
  • Models, Molecular
  • Oxidants
  • Oxidation-Reduction
  • Oxygen
  • Protein Conformation
  • Singlet Oxygen
  • Spectrometry, Mass, Electrospray Ionization
  • Thermodynamics
  • Tryptophan
  • Ultraviolet Rays
  • Water
  • Xenon
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Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1062722

PubMed ID

  • 11546867
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Additional Document Info

start page

  • 1806

end page

  • 1811

volume

  • 293

issue

  • 5536

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