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Antibody Catalysis of the Oxidation of Water

Wentworth, Paul Jr. and Jones, Lyn H. and Wentworth, Anita D. and Zhu, Xueyong and Larsen, Nicholas A. and Wilson, Ian A. and Xu, Xin and Goddard, William A., III and Janda, Kim D. and Eschenmoser, Albert and Lerner, Richard A. (2001) Antibody Catalysis of the Oxidation of Water. Science, 293 (5536). pp. 1806-1811. ISSN 0036-8075. https://resolver.caltech.edu/CaltechAUTHORS:20141118-125124794

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.sciencemag.org/content/293/5536/1806.abstractPublisherArticle
http://dx.doi.org/10.1126/science.1062722DOIArticle
ORCID:
AuthorORCID
Goddard, William A., III0000-0003-0097-5716
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.).
Funders:
Funding AgencyGrant Number
NIHGM43858
NIHCA27489
NIHHD 36385
Other Numbering System:
Other Numbering System NameOther Numbering System ID
WAG0466
Issue or Number:5536
Record Number:CaltechAUTHORS:20141118-125124794
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141118-125124794
Official Citation:Antibody Catalysis of the Oxidation of Water Paul Wentworth Jr., Lyn H. Jones, Anita D. Wentworth, Xueyong Zhu, Nicholas A. Larsen, Ian A. Wilson, Xin Xu, William A. Goddard III, Kim D. Janda, Albert Eschenmoser, and Richard A. Lerner Science 7 September 2001: 293 (5536), 1806-1811. [DOI:10.1126/science.1062722]
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51907
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:18 Nov 2014 21:47
Last Modified:03 Oct 2019 07:37

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