35C8

CATALYTIC ANTIBODY 5C8, FAB-INHIBITOR COMPLEX

35C8 の概要

• エントリーDOI: 10.2210/pdb35c8/pdb
• 分子名称: IGG 5C8, N-(PARA-GLUTARAMIDOPHENYL-ETHYL)-PIPERIDINIUM-N-OXIDE, ... (4 entities in total)
• 機能のキーワード: catalytic antibody, fab, ring closure reaction
• 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: 46580.55

構造登録者

Gruber, K.,Wilson, I.A. (登録日: 1998-03-18, 公開日: 1999-03-23, 最終更新日: 2024-10-16)

主引用文献

Gruber, K.,Zhou, B.,Houk, K.N.,Lerner, R.A.,Shevlin, C.G.,Wilson, I.A.
Structural basis for antibody catalysis of a disfavored ring closure reaction.
Biochemistry, 38:7062-7074, 1999

PubMed Abstract: The catalysis of disfavored chemical reactions, especially those with no known natural enzyme counterparts, is one of the most promising achievements of catalytic antibody research. Antibodies 5C8, 14B9, 17F6, and 26D9, elicited by two different transition-state analogues, catalyze disfavored endo-tet cyclization reactions of trans-epoxy alcohols, in formal violation of Baldwin's rules for ring closure. Thus far, neither chemical nor enzyme catalysis has been capable of emulating the extraordinary activity and specificity of these antibodies. X-ray structures of two complexes of Fab 5C8 with the original hapten and with an inhibitor have been determined to 2.0 A resolution. The Fab structure has an active site that contains a putative catalytic diad, consisting of AspH95 and HisL89, capable of general acid/base catalysis. The stabilization of a positive charge that develops along the reaction coordinate appears to be an important factor for rate enhancement and for directing the reaction along the otherwise disfavored pathway. Sequence analysis of the four catalytic antibodies, as well as four inactive antibodies that strongly bind the transition-state analogues, suggests a conserved catalytic mechanism. The occurrence of the putative base HisL89 in all active antibodies, its absence in three out of the four analyzed inactive antibodies, and the rarity of a histidine at this position in immunoglobulins support an important catalytic role for this residue.

PubMed: 10353817
DOI: 10.1021/bi990210s

実験手法

X-RAY DIFFRACTION (2 Å)