1GAF

48G7 HYBRIDOMA LINE FAB COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID

1GAF の概要

• エントリーDOI: 10.2210/pdb1gaf/pdb
• 分子名称: CHIMERIC 48G7 FAB, 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID, ... (4 entities in total)
• 機能のキーワード: ester hydrolysis, esterolytic, fab, catalytic antibody
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46996.26

構造登録者

Wedemayer, G.J.,Patten, P.A.,Stevens, R.C.,Schultz, P.G. (登録日: 1996-02-06, 公開日: 1996-07-11, 最終更新日: 2024-11-20)

主引用文献

Patten, P.A.,Gray, N.S.,Yang, P.L.,Marks, C.B.,Wedemayer, G.J.,Boniface, J.J.,Stevens, R.C.,Schultz, P.G.
The immunological evolution of catalysis.
Science, 271:1086-1091, 1996

PubMed Abstract: The germline genes used by the mouse to generate the esterolytic antibody 48G7 were cloned and expressed in an effort to increase our understanding of the detailed molecular mechanisms by which the immune system evolves catalytic function. The nine replacement mutations that were fixed during affinity maturation increased affinity for the transition state analogue by a factor of 10(4), primarily the result of a decrease in the dissociation rate of the hapten-antibody complex. There was a corresponding increase in the rate of reaction of antibody with substrate, k(cat)/k(m), from 1.7 x 10(2)M(-1) min(-1) to 1.4 x 10(4)M(-1) min(-1). The three-dimensional crystal structure of the 48G7-transition state analogue complex at 2.0 angstroms resolution indicates that one of the nine residues in which somatic mutations have been fixed directly contact the hapten. Thus, in the case of 48G7, affinity maturation appears to play a conformational role, either in reorganizing the active site geometry of limiting side-chain and backbone flexibility of the germline antibody. The crystal structure and analysis of somatic and directed active site mutants underscore the role of transition state stabilization in the evolution of this catalytic antibody.

PubMed: 8599084

実験手法

X-RAY DIFFRACTION (1.95 Å)