title: Antibody catalysis of the oxidation of water.
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.
authors.affiliation: Department of Chemistry, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wentworth
authors.forename: L H
authors.initials: LH
authors.lastname: Jones
authors.forename: A D
authors.initials: AD
authors.lastname: Wentworth
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: N A
authors.initials: NA
authors.lastname: Larsen
authors.forename: I A
authors.initials: IA
authors.lastname: Wilson
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: W A
authors.initials: WA
authors.lastname: Goddard
authors.forename: K D
authors.initials: KD
authors.lastname: Janda
authors.forename: A
authors.initials: A
authors.lastname: Eschenmoser
authors.forename: R A
authors.initials: RA
authors.lastname: Lerner
mesh_terms: D000818:Animals; D017151:Antibodies, Catalytic / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D016877:Oxidants / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D011487:Protein Conformation; D026082:Singlet Oxygen; D021241:Spectrometry, Mass, Electrospray Ionization; D013816:Thermodynamics; D014364:Tryptophan / Q000378:metabolism; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry* / Q000378:metabolism*; D014978:Xenon / Q000378:metabolism
chemical_list: D017151:Antibodies, Catalytic; D016877:Oxidants; D014867:Water; D026082:Singlet Oxygen; D014978:Xenon; D014364:Tryptophan; D006861:Hydrogen Peroxide; D010100:Oxygen