Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S

Nature Communications
Beatriz TrastoyMarcelo E Guerin

Abstract

Endoglycosidase S (EndoS) is a bacterial endo-β-N-acetylglucosaminidase that specifically catalyzes the hydrolysis of the β-1,4 linkage between the first two N-acetylglucosamine residues of the biantennary complex-type N-linked glycans of IgG Fc regions. It is used for the chemoenzymatic synthesis of homogeneously glycosylated antibodies with improved therapeutic properties, but the molecular basis for its substrate specificity is unknown. Here, we report the crystal structure of the full-length EndoS in complex with its oligosaccharide G2 product. The glycoside hydrolase domain contains two well-defined asymmetric grooves that accommodate the complex-type N-linked glycan antennae near the active site. Several loops shape the glycan binding site, thereby governing the strict substrate specificity of EndoS. Comparing the arrangement of these loops within EndoS and related endoglycosidases, reveals distinct-binding site architectures that correlate with the respective glycan specificities, providing a basis for the bioengineering of endoglycosidases to tailor the chemoenzymatic synthesis of monoclonal antibodies.

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Citations

Oct 17, 2019·Glycobiology·Jonathan SjögrenAndreas Nägeli
Feb 16, 2020·Nature Communications·Beatriz TrastoyMarcelo E Guerin
Jul 30, 2021·The Journal of Biological Chemistry·Beatriz TrastoyMarcelo E Guerin
Jul 27, 2021·PLoS Computational Biology·Asaminew H AytenfisuAlexander D MacKerell
Aug 25, 2018·Chemical Reviews·Chao Li, Lai-Xi Wang
Aug 17, 2021·Frontiers in Neuroanatomy·Md Mahmudul HasanMitsutoshi Setou
Feb 5, 2019·Journal of the American Chemical Society·Larissa Krasnova, Chi-Huey Wong

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Methods Mentioned

BETA
glycosylation
X-ray
size-exclusion chromatography
gel filtration
PCR
transfection

Software Mentioned

Chimera
PHENIX
PRIMUS
EndoBT
Buccaneer
DALI
SREFLEX
BoxShade
UCSF Chimera package
Coot

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