8UEN

Crystal structure of Corynebacterium ulcerans endo-beta-N-acetylglucosaminidase catalytically inactive CU43 D187A-E189A at 2.3 A (P 21 21 2)

8UEN の概要

• エントリーDOI: 10.2210/pdb8uen/pdb
• 分子名称: Corynebacterial protease CP40 (2 entities in total)
• 機能のキーワード: secreted endo-beta-n-acetylglucosaminidase, cu43, igg-specific, hydrolase
• 由来する生物種: Corynebacterium ulcerans
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92214.62

構造登録者

Sastre, D.E.,Sultana, N.,Sundberg, E.J. (登録日: 2023-10-02, 公開日: 2024-10-16, 最終更新日: 2024-12-11)

主引用文献

Sastre, D.E.,Bournazos, S.,Du, J.,Boder, E.J.,Edgar, J.E.,Azzam, T.,Sultana, N.,Huliciak, M.,Flowers, M.,Yoza, L.,Xu, T.,Chernova, T.A.,Ravetch, J.V.,Sundberg, E.J.
Potent efficacy of an IgG-specific endoglycosidase against IgG-mediated pathologies.
Cell, 187:6994-, 2024

PubMed Abstract: Endo-β-N-acetylglucosaminidases (ENGases) that specifically hydrolyze the Asn297-linked glycan on immunoglobulin G (IgG) antibodies, the major molecular determinant of fragment crystallizable (Fc) γ receptor (FcγR) binding, are exceedingly rare. All previously characterized IgG-specific ENGases are multi-domain proteins secreted as an immune evasion strategy by Streptococcus pyogenes strains. Here, using in silico analysis and mass spectrometry techniques, we identified a family of single-domain ENGases secreted by pathogenic corynebacterial species that exhibit strict specificity for IgG antibodies. By X-ray crystallographic and surface plasmon resonance analyses, we found that the most catalytically efficient IgG-specific ENGase family member recognizes both protein and glycan components of IgG. Employing in vivo models, we demonstrated the remarkable efficacy of this IgG-specific ENGase in mitigating numerous pathologies that rely on FcγR-mediated effector functions, including T and B lymphocyte depletion, autoimmune hemolytic anemia, and antibody-dependent enhancement of dengue disease, revealing its potential for treating and/or preventing a wide range of IgG-mediated diseases in humans.

PubMed: 39437779
DOI: 10.1016/j.cell.2024.09.038

実験手法

X-RAY DIFFRACTION (2.3 Å)