3AAZ

Crystal structure of the humanized recombinant Fab fragment of a murine; antibody

3AAZ の概要

• エントリーDOI: 10.2210/pdb3aaz/pdb
• 分子名称: Humanized recombinant Fab fragment of a murine; antibody (3 entities in total)
• 機能のキーワード: antibody engineering, humanization, hwo-2 fab, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 100005.98

構造登録者

Streltsov, V.A. (登録日: 2009-11-28, 公開日: 2010-03-02, 最終更新日: 2024-10-16)

主引用文献

Robert, R.,Streltsov, V.A.,Newman, J.,Pearce, L.A.,Wark, K.L.,Dolezal, O.
Germline humanization of a murine Abeta antibody and crystal structure of the humanized recombinant Fab fragment.
Protein Sci., 19:299-308, 2010

PubMed Abstract: Alzheimer's disease is the most common form of dementia, affecting 26 million people worldwide. The Abeta peptide (39-43 amino acids) derived from the proteolytic cleavage of the amyloid precursor protein is one of the main constituents of amyloid plaques associated with disease pathogenesis and therefore a validated target for therapy. Recently, we characterized antibody fragments (Fab and scFvs) derived from the murine monoclonal antibody WO-2, which bind the immunodominant epitope ((3)EFRH(6)) in the Abeta peptide at the N-terminus. In vitro, these fragments are able to inhibit fibril formation, disaggregate preformed amyloid fibrils, and protect neuroblastoma cells against oligomer-mediated toxicity. In this study, we describe the humanization of WO-2 using complementary determining region loop grafting onto the human germline gene and the determination of the three-dimensional structure by X-ray crystallography. This humanized version retains a high affinity for the Abeta peptide and therefore is a potential candidate for passive immunotherapy of Alzheimer's disease.

PubMed: 20014445
DOI: 10.1002/pro.312

実験手法

X-RAY DIFFRACTION (2.2 Å)