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

DOI: 10.1038/s41467-018-04300-x DOI Help

Authors: Beatriz Trastoy (CIC bioGUNE) , Erik Klontz (University of Maryland School of Medicine) , Jared Orwenyo (University of Maryland) , Alberto Marina (CIC bioGUNE) , Lai-Xi Wang (University of Maryland) , Eric J. Sundberg (University of Maryland School of Medicine) , Marcelo E. Guerin (CIC bioGUNE; Unidad de Biofísica; Universidad del País Vasco; IKERBASQUE)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: May 2018
Diamond Proposal Number(s): 15304

Open Access Open Access

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.

Journal Keywords: Antibody therapy; Enzymes; Glycobiology; X-ray crystallography

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials

Instruments: B21-High Throughput SAXS

Other Facilities: SOLEIL

Added On: 21/05/2018 09:25


Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)