1YEJ

CATALYTIC ANTIBODY COMPLEX

1YEJ の概要

• エントリーDOI: 10.2210/pdb1yej/pdb
• 分子名称: PROTEIN (IG ANTIBODY D2.3 (LIGHT CHAIN)), PROTEIN (IG ANTIBODY D2.3 (HEAVY CHAIN)), ZINC ION, ... (5 entities in total)
• 機能のキーワード: abzyme, transition state analog, 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: 49069.26

構造登録者

Gigant, B.,Knossow, M. (登録日: 1998-08-13, 公開日: 1999-01-13, 最終更新日: 2024-10-30)

主引用文献

Gigant, B.,Charbonnier, J.B.,Eshhar, Z.,Green, B.S.,Knossow, M.
Crossreactivity, efficiency and catalytic specificity of an esterase-like antibody.
J.Mol.Biol., 284:741-750, 1998

PubMed Abstract: The antibody D2.3 catalyzes the hydrolysis of several p-nitrobenzyl and p-nitrophenyl esters with significant rate enhancement; product inhibition is observed with the former compounds but not with the latter. Whereas enzyme specificity has been extensively studied by X-ray crystallography, structural data on catalytic antibodies have thus far related only to one of the reactions they catalyze. To investigate the substrate specificity and the substrate relative to product selectivity of D2.3, we have determined the structures of its complexes with two p-nitrophenyl phosphonate transition state analogs (TSAs) and with the reaction product, p-nitrophenol. The complexes with these TSAs, determined at 1.9 A resolution, and that with p-nitrobenzyl phosphonate determined previously, differ mainly by the locations and conformations of the ligands. Taken together with kinetic data, the structures suggest that a hydrogen bond to an atom of the substrate distant by eight covalent bonds from the carbonyl group of the hydrolyzed ester bond contributes to catalytic efficiency and substrate specificity. The structure of Fab D2.3 complexed with p-nitrophenol was determined at 2.1 A resolution. Release of p-nitrophenol is facilitated due to the unfavourable interaction of the partial charge of the nitro group of p-nitrophenolate with the hydrophobic cavity where it is located, and to the absence of a direct hydrogen bond between the product and the Fab. Catalytic specificity and the manner of product release are both affected by interactions with substrate atoms remote from the reaction center that were not programmed in the design of the TSA used to elicit this antibody. Selection of a catalytic antibody that makes use of TSA unprogrammed features has been made practical because of the screening for catalytic efficiency incorporated in the procedure used to obtain it.

PubMed: 9826512
DOI: 10.1006/jmbi.1998.2198

実験手法

X-RAY DIFFRACTION (1.85 Å)