1EAP

CRYSTAL STRUCTURE OF A CATALYTIC ANTIBODY WITH A SERINE PROTEASE ACTIVE SITE

1EAP の概要

• エントリーDOI: 10.2210/pdb1eap/pdb
• 分子名称: IGG2B-KAPPA 17E8 FAB (LIGHT CHAIN), IGG2B-KAPPA 17E8 FAB (HEAVY CHAIN), PHENYL[1-(N-SUCCINYLAMINO)PENTYL]PHOSPHONATE (3 entities in total)
• 機能のキーワード: catalytic antibody
• 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: 46758.03

構造登録者

Zhou, G.W.,Guo, J.,Huang, W.,Scanlan, T.S.,Fletterick, R.J. (登録日: 1994-08-10, 公開日: 1994-12-20, 最終更新日: 2024-10-09)

主引用文献

Zhou, G.W.,Guo, J.,Huang, W.,Scanlan, T.S.,Fletterick, R.J.
Crystal structure of a catalytic antibody with a serine protease active site.
Science, 265:1059-1064, 1994

PubMed Abstract: The three-dimensional structure of an unusually active hydrolytic antibody with a phosphonate transition state analog (hapten) bound to the active site has been solved to 2.5 A resolution. The antibody (17E8) catalyzes the hydrolysis of norleucine and methionine phenyl esters and is selective for amino acid esters that have the natural alpha-carbon L configuration. A plot of the pH-dependence of the antibody-catalyzed reaction is bell-shaped with an activity maximum at pH 9.5; experiments on mechanism lend support to the formation of a covalent acyl-antibody intermediate. The structural and kinetic data are complementary and support a hydrolytic mechanism for the antibody that is remarkably similar to that of the serine proteases. The antibody active site contains a Ser-His dyad structure proximal to the phosphorous atom of the bound hapten that resembles two of the three components of the Ser-His-Asp catalytic triad of serine proteases. The antibody active site also contains a Lys residue to stabilize oxyanion formation, and a hydrophobic binding pocket for specific substrate recognition of norleucine and methionine side chains. The structure identifies active site residues that mediate catalysis and suggests specific mutations that may improve the catalytic efficiency of the antibody. This high resolution structure of a catalytic antibody-hapten complex shows that antibodies can converge on active site structures that have arisen through natural enzyme evolution.

PubMed: 8066444

実験手法

X-RAY DIFFRACTION (2.4 Å)