1RUR

Crystal Structure (I) of native Diels-Alder antibody 13G5 Fab at pH 8.0 with a data set collected at SSRL beamline 9-1.

Summary for 1RUR

• Entry DOI: 10.2210/pdb1rur/pdb
• Related: 1RUQ
• Descriptor: immunoglobulin 13G5, light chain, immunoglobulin 13G5, heavy chain, ZINC ION, ... (4 entities in total)
• Functional Keywords: immunoglobulin, catalytic antibody, water oxidation, amino acid modification, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 47138.07

Authors

Zhu, X.,Wentworth Jr., P.,Wentworth, A.D.,Eschenmoser, A.,Lerner, R.A.,Wilson, I.A. (deposition date: 2003-12-11, release date: 2004-03-02, Last modification date: 2024-10-30)

Primary citation

Zhu, X.,Wentworth Jr., P.,Wentworth, A.D.,Eschenmoser, A.,Lerner, R.A.,Wilson, I.A.
Probing the antibody-catalyzed water-oxidation pathway at atomic resolution.
Proc.Natl.Acad.Sci.USA, 110:2247-2252, 2004

PubMed Abstract: Antibodies can catalyze the generation of hydrogen peroxide (H2O2) from singlet dioxygen (1O2*) and water via the postulated intermediacy of dihydrogen trioxide (H2O3) and other trioxygen species. Nine different crystal structures were determined to elucidate the chemical consequences to the antibody molecule itself of exposure to such reactive intermediates and to provide insights into the location on the antibody where these species could be generated. Herein, we report structural evidence for modifications of two specific antibody residues within the interfacial region of the variable and constant domains of different murine antibody antigen-binding fragments (Fabs) by reactive species generated during the antibody-catalyzed water oxidation process. Crystal structure analyses of murine Fabs 4C6 and 13G5 after UV-irradiation revealed complex oxidative modifications to tryptophan L163 and, in 4C6, hydroxylation of the Cgamma of glutamine H6. These discrete modifications of specific residues add further support for the "active site" of the water-oxidation pathway being located within the interfacial region of the constant and variable domains and highlight the general resistance of the antibody molecule to oxidation by reactive oxygen species generated during the water-oxidation process.

PubMed: 14982995
DOI: 10.1073/pnas.0307311101

Experimental method

X-RAY DIFFRACTION (1.5 Å)