7O4W

Crystal structure of diphtheria toxin mutant CRM197 with a disulphide bond replaced by a Cys-Acetone-Cys bridge

7O4W の概要

• エントリーDOI: 10.2210/pdb7o4w/pdb
• 分子名称: Diphtheria toxin, 1-hydroxypropan-2-one, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: diphtheria toxin, mutant, disulphide bridge, modified disulphide bridge, acetone., toxin
• 由来する生物種: Corynebacterium diphtheriae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 59103.09

構造登録者

Veggi, D.,Dello Iacono, L. (登録日: 2021-04-07, 公開日: 2022-04-06, 最終更新日: 2024-01-31)

主引用文献

Carboni, F.,Kitowski, A.,Sorieul, C.,Veggi, D.,Marques, M.C.,Oldrini, D.,Balducci, E.,Brogioni, B.,Del Bino, L.,Corrado, A.,Angiolini, F.,Dello Iacono, L.,Margarit, I.,Romano, M.R.,Bernardes, G.J.L.,Adamo, R.
Retaining the structural integrity of disulfide bonds in diphtheria toxoid carrier protein is crucial for the effectiveness of glycoconjugate vaccine candidates.
Chem Sci, 13:2440-2449, 2022

PubMed Abstract: The introduction of glycoconjugate vaccines marks an important point in the fight against various infectious diseases. The covalent conjugation of relevant polysaccharide antigens to immunogenic carrier proteins enables the induction of a long-lasting and robust IgG antibody response, which is not observed for pure polysaccharide vaccines. Although there has been remarkable progress in the development of glycoconjugate vaccines, many crucial parameters remain poorly understood. In particular, the influence of the conjugation site and strategy on the immunogenic properties of the final glycoconjugate vaccine is the focus of intense research. Here, we present a comparison of two cysteine selective conjugation strategies, elucidating the impact of both modifications on the structural integrity of the carrier protein, as well as on the immunogenic properties of the resulting glycoconjugate vaccine candidates. Our work suggests that conjugation chemistries impairing structurally relevant elements of the protein carrier, such as disulfide bonds, can have a dramatic effect on protein immunogenicity.

PubMed: 35310500
DOI: 10.1039/d1sc01928g

実験手法

X-RAY DIFFRACTION (2.03002061079 Å)