1A3L

CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION

1A3L の概要

• エントリーDOI: 10.2210/pdb1a3l/pdb
• 分子名称: IMMUNOGLOBULIN FAB 13G5 (LIGHT CHAIN), IMMUNOGLOBULIN FAB 13G5 (HEAVY CHAIN), 1-CARBOXY-1'-[(DIMETHYLAMINO)-CARBONYL]FERROCENE, ... (4 entities in total)
• 機能のキーワード: diels-alder, disfavored reaction, catalytic antibody, immunoglobulin
• 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: 47308.37

構造登録者

Heine, A.,Wilson, I.A. (登録日: 1998-01-22, 公開日: 1999-02-16, 最終更新日: 2024-10-30)

主引用文献

Heine, A.,Stura, E.A.,Yli-Kauhaluoma, J.T.,Gao, C.,Deng, Q.,Beno, B.R.,Houk, K.N.,Janda, K.D.,Wilson, I.A.
An antibody exo Diels-Alderase inhibitor complex at 1.95 angstrom resolution.
Science, 279:1934-1940, 1998

PubMed Abstract: A highly specific Diels-Alder protein catalyst was made by manipulating the antibody repertoire of the immune system. The catalytic antibody 13G5 catalyzes a disfavored exo Diels-Alder transformation in a reaction for which there is no natural enzyme counterpart and that yields a single regioisomer in high enantiomeric excess. The crystal structure of the antibody Fab in complex with a ferrocenyl inhibitor containing the essential haptenic core that elicited 13G5 was determined at 1.95 angstrom resolution. Three key antibody residues appear to be responsible for the observed catalysis and product control. Tyrosine-L36 acts as a Lewis acid activating the dienophile for nucleophilic attack, and asparagine-L91 and aspartic acid-H50 form hydrogen bonds to the carboxylate side chain that substitutes for the carbamate diene substrate. This hydrogen-bonding scheme leads to rate acceleration and also pronounced stereoselectivity. Docking experiments with the four possible ortho transition states of the reaction explain the specific exo effect and suggest that the (3R,4R)-exo stereoisomer is the preferred product.

PubMed: 9506943
DOI: 10.1126/science.279.5358.1934

実験手法

X-RAY DIFFRACTION (1.95 Å)