2J88

Hyaluronidase in complex with a monoclonal IgG Fab fragment

2J88 の概要

• エントリーDOI: 10.2210/pdb2j88/pdb
• 関連するPDBエントリー: 1FCQ 1FCU 1FCV
• 分子名称: HYALURONONGLUCOSAMINIDASE, FAB, ... (4 entities in total)
• 機能のキーワード: glycoprotein, glycosidase family 56, zymogen, allergen, 7- stranded (beta/alpha) tim barrel, hydrolase, glycosidase, immunoglobulin domain
• 由来する生物種: APIS MELLIFERA (HONEY BEE); 詳細
• 細胞内の位置: Secreted: Q08169
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 85001.18

構造登録者

Padavattan, S.,Schirmer, T.,Markovic-Housley, Z. (登録日: 2006-10-23, 公開日: 2007-04-03, 最終更新日: 2024-10-09)

主引用文献

Padavattan, S.,Schirmer, T.,Schmidt, M.,Akdis, C.,Valenta, R.,Mittermann, I.,Soldatova, L.,Slater, J.,Mueller, U.,Markovic-Housley, Z.
Identification of a B-Cell Epitope of Hyaluronidase, a Major Bee Venom Allergen, from its Crystal Structure in Complex with a Specific Fab.
J.Mol.Biol., 368:742-, 2007

PubMed Abstract: The major allergens of honeybee venom, hyaluronidase (Hyal) and phospholipase A2, can induce life-threatening IgE-mediated allergic reactions in humans. Although conventional immunotherapy is effective, up to 40% of patients develop allergic side effects including anaphylaxis and thus, there is a need for an improved immunotherapy. A murine monoclonal anti-Hyal IgG1 antibody (mAb 21E11), that competed for Hyal binding with IgEs from sera of bee venom allergic patients, was raised. The fragment of these IgG antibodies which bind to antigen (Fab) was produced and complexed (1:1) with Hyal. The crystal structure determination of Hyal/Fab 21E11 complex (2.6 A) enabled the identification of the Hyal-IgG interface which provides indirect information on the Hyal-IgE interaction (B-cell epitope). The epitope is composed of a linear array of nine residues (Arg138, His141-Arg148) located at the tip of a helix-turn-helix motive which protrudes away from the globular core and fits tightly into the deep surface pocket formed by the residues from the six complementarity determining regions (CDRs) of the Fab. The epitope is continuous and yet its conformation appears to be essential for Ab recognition, since the synthetic 15-mer peptide comprising the entire epitope (Arg138-Glu152) is neither recognized by mAb 21E11 nor by human IgEs. The structure of the complex provides the basis for the rational design of Hyal derivatives with reduced allergenic activity, which could be used in the development of safer allergen-specific immunotherapy.

PubMed: 17374540
DOI: 10.1016/J.JMB.2007.02.036

実験手法

X-RAY DIFFRACTION (2.6 Å)