1Y18

Fab fragment of catalytic elimination antibody 34E4 E(H50)D mutant in complex with hapten

1Y18 の概要

• エントリーDOI: 10.2210/pdb1y18/pdb
• 関連するPDBエントリー: 1Y0L
• 分子名称: Catalytic antibody 34E4 light chain, Catalytic antibody 34E4 heavy chain, 2-AMINO-5,6-DIMETHYL-BENZIMIDAZOLE-1-PENTANOIC ACID, ... (5 entities in total)
• 機能のキーワード: immunoglobulin, catalytic antibody, chimeric fab, hapten complex, immune system
• 由来する生物種: Mus musculus, Homo sapiens (house mouse, human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 192406.83

構造登録者

Debler, E.W.,Ito, S.,Heine, A.,Wilson, I.A. (登録日: 2004-11-17, 公開日: 2005-04-05, 最終更新日: 2024-10-30)

主引用文献

Debler, E.W.,Ito, S.,Seebeck, F.P.,Heine, A.,Hilvert, D.,Wilson, I.A.
Structural origins of efficient proton abstraction from carbon by a catalytic antibody
Proc.Natl.Acad.Sci.USA, 102:4984-4989, 2005

PubMed Abstract: Antibody 34E4 catalyzes the conversion of benzisoxazoles to salicylonitriles with high rates and multiple turnovers. The crystal structure of its complex with the benzimidazolium hapten at 2.5-angstroms resolution shows that a combination of hydrogen bonding, pi stacking, and van der Waals interactions is exploited to position both the base, Glu(H50), and the substrate for efficient proton transfer. Suboptimal placement of the catalytic carboxylate, as observed in the 2.8-angstroms structure of the Glu(H50)Asp variant, results in substantially reduced catalytic efficiency. In addition to imposing high positional order on the transition state, the antibody pocket provides a highly structured microenvironment for the reaction in which the carboxylate base is activated through partial desolvation, and the highly polarizable transition state is stabilized by dispersion interactions with the aromatic residue Trp(L91) and solvation of the leaving group oxygen by external water. The enzyme-like efficiency of general base catalysis in this system directly reflects the original hapten design, in which a charged guanidinium moiety was strategically used to elicit an accurately positioned functional group in an appropriate reaction environment and suggests that even larger catalytic effects may be achievable by extending this approach to the induction of acid-base pairs capable of bifunctional catalysis.

PubMed: 15788533
DOI: 10.1073/pnas.0409207102

実験手法

X-RAY DIFFRACTION (2.8 Å)