3FO2

Crystal structure of hapten complex of catalytic elimination antibody 13G5 (Glu(L39)Gln mutant)

3FO2 の概要

• エントリーDOI: 10.2210/pdb3fo2/pdb
• 関連するPDBエントリー: 2GJZ 2GK0 3FO0 3FO1
• 分子名称: Catalytic antibody Fab 13G5 kappa light chain chimera, Catalytic antibody Fab 13G5 IgG2b heavy chain chimera, 5-[(2-AMINO-1H-BENZIMIDAZOL-6-YL)AMINO]-5-OXOPENTANOIC ACID, ... (4 entities in total)
• 機能のキーワード: immunoglobulin, catalytic antibody, chimeric fab, hapten complex, acid base catalysis, proton transfer, immunoglobulin domain, immune system
• 由来する生物種: Mus musculus, Homo sapiens (Mouse, Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 97120.56

構造登録者

Debler, E.W.,Wilson, I.A. (登録日: 2008-12-27, 公開日: 2009-11-10, 最終更新日: 2024-10-30)

主引用文献

Debler, E.W.,Muller, R.,Hilvert, D.,Wilson, I.A.
An aspartate and a water molecule mediate efficient acid-base catalysis in a tailored antibody pocket.
Proc.Natl.Acad.Sci.USA, 106:18539-18544, 2009

PubMed Abstract: Design of catalysts featuring multiple functional groups is a desirable, yet formidable goal. Antibody 13G5, which accelerates the cleavage of unactivated benzisoxazoles, is one of few artificial enzymes that harness an acid and a base to achieve efficient proton transfer. X-ray structures of the Fab-hapten complexes of wild-type 13G5 and active-site variants now afford detailed insights into its mechanism. The parent antibody preorganizes Asp(H35) and Glu(L34) to abstract a proton from substrate and to orient a water molecule for leaving group stabilization, respectively. Remodeling the environment of the hydrogen bond donor with a compensatory network of ordered waters, as seen in the Glu(L34) to alanine mutant, leads to an impressive 10(9)-fold rate acceleration over the nonenzymatic reaction with acetate, illustrating the utility of buried water molecules in bifunctional catalysis. Generalization of these design principles may aid in creation of catalysts for other important chemical transformations.

PubMed: 19846764
DOI: 10.1073/pnas.0902700106

実験手法

X-RAY DIFFRACTION (2.18 Å)