1RUP

Crystal structure (G) of native cationic cyclization antibody 4C6 fab at pH 8.5 with a data set collected at APS beamline 19-ID

1RUP の概要

• エントリーDOI: 10.2210/pdb1rup/pdb
• 関連するPDBエントリー: 1NCW 1ND0 1ru9 1rua 1ruk 1rul 1rum
• 分子名称: immunoglobulin igg2a, heavy chain, immunoglobulin igg2a, light chain, BENZOIC ACID, ... (5 entities in total)
• 機能のキーワード: immunoglobulin, catalytic antibody, water oxidation, amino acid modification, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48526.10

構造登録者

Zhu, X.,Wentworth Jr., P.,Wentworth, A.D.,Eschenmoser, A.,Lerner, R.A.,Wilson, I.A. (登録日: 2003-12-11, 公開日: 2004-03-02, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.4 Å)