6E58

Crystal structure of Streptococcus pyogenes endo-beta-N-acetylglucosaminidase (EndoS2)

6E58 の概要

• エントリーDOI: 10.2210/pdb6e58/pdb
• 分子名称: Secreted Endo-beta-N-acetylglucosaminidase (EndoS), CALCIUM ION (3 entities in total)
• 機能のキーワード: glycoside hydrolase, endo-beta-n-acetylglucosaminidase s2, endoglycosidase s2, endos2, hydrolase
• 由来する生物種: Streptococcus pyogenes M49 591
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 181844.70

構造登録者

Klontz, E.H.,Trastoy, B.,Gunther, S.,Guerin, M.E.,Sundberg, E.J. (登録日: 2018-07-19, 公開日: 2019-02-06, 最終更新日: 2023-10-11)

主引用文献

Klontz, E.H.,Trastoy, B.,Deredge, D.,Fields, J.K.,Li, C.,Orwenyo, J.,Marina, A.,Beadenkopf, R.,Gunther, S.,Flores, J.,Wintrode, P.L.,Wang, L.X.,Guerin, M.E.,Sundberg, E.J.
Molecular Basis of Broad SpectrumN-Glycan Specificity and Processing of Therapeutic IgG Monoclonal Antibodies by Endoglycosidase S2.
ACS Cent Sci, 5:524-538, 2019

PubMed Abstract: Immunoglobulin G (IgG) glycosylation critically modulates antibody effector functions. secretes a unique endo-β--acetylglucosaminidase, EndoS2, which deglycosylates the conserved -linked glycan at Asn297 on IgG Fc to eliminate its effector functions and evade the immune system. EndoS2 and specific point mutants have been used to chemoenzymatically synthesize antibodies with customizable glycosylation for gain of functions. EndoS2 is useful in these schemes because it accommodates a broad range of -glycans, including high-mannose, complex, and hybrid types; however, its mechanism of substrate recognition is poorly understood. We present crystal structures of EndoS2 alone and bound to complex and high-mannose glycans; the broad -glycan specificity is governed by critical loops that shape the binding site of EndoS2. Furthermore, hydrolytic experiments, domain-swap chimeras, and hydrogen-deuterium exchange mass spectrometry reveal the importance of the carbohydrate-binding module in the mechanism of IgG recognition by EndoS2, providing insights into engineering enzymes to catalyze customizable glycosylation reactions.

PubMed: 30937380
DOI: 10.1021/acscentsci.8b00917

実験手法

X-RAY DIFFRACTION (2.75 Å)