8A64

cryoEM structure of the catalytically inactive EndoS from S. pyogenes in complex with the Fc region of immunoglobulin G1.

これはPDB形式変換不可エントリーです。

8A64 の概要

• エントリーDOI: 10.2210/pdb8a64/pdb
• EMDBエントリー: 15205
• 分子名称: Endo-beta-N-acetylglucosaminidase F2, Immunoglobulin gamma-1 heavy chain, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: endoglycosidase s, endos, endo-b-n-acetylglucosaminidase, fc region, antibody, immunoglobulin g1, streptococcus pyogenes, n-glycans, hydrolase
• 由来する生物種: Streptococcus pyogenes; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 207656.86

構造登録者

Trastoy, B.,Cifuente, J.O.,Du, J.J.,Sundberg, E.J.,Guerin, M.E. (登録日: 2022-06-16, 公開日: 2023-04-05, 最終更新日: 2024-11-20)

主引用文献

Trastoy, B.,Du, J.J.,Cifuente, J.O.,Rudolph, L.,Garcia-Alija, M.,Klontz, E.H.,Deredge, D.,Sultana, N.,Huynh, C.G.,Flowers, M.W.,Li, C.,Sastre, D.E.,Wang, L.X.,Corzana, F.,Mallagaray, A.,Sundberg, E.J.,Guerin, M.E.
Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases.
Nat Commun, 14:1705-1705, 2023

PubMed Abstract: Bacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Streptococcus pyogenes serotypes secrete two multi-modular endo-β-N-acetylglucosaminidases, EndoS and EndoS2, that specifically deglycosylate the conserved N-glycan at Asn297 on IgG Fc, disabling antibody-mediated effector functions. Amongst thousands of known carbohydrate-active enzymes, EndoS and EndoS2 represent just a handful of enzymes that are specific to the protein portion of the glycoprotein substrate, not just the glycan component. Here, we present the cryoEM structure of EndoS in complex with the IgG1 Fc fragment. In combination with small-angle X-ray scattering, alanine scanning mutagenesis, hydrolytic activity measurements, enzyme kinetics, nuclear magnetic resonance and molecular dynamics analyses, we establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by EndoS and EndoS2. Our results provide a rational basis from which to engineer novel enzymes with antibody and glycan selectivity for clinical and biotechnological applications.

PubMed: 36973249
DOI: 10.1038/s41467-023-37215-3

実験手法

ELECTRON MICROSCOPY (4.6 Å)