Structural basis for the recognition of complex-Type N-glycans by Endoglycosidase S
PublisherNature Publishing Group
MetadataShow full item record
AbstractEndoglycosidase 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. Copyright 2018 The Author(s).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85047013840&doi=10.1038%2fs41467-018-04300-x&partnerID=40&md5=df7734109c4bfdf1c26f8df022663820; http://hdl.handle.net/10713/9197
- EndoS2 is a unique and conserved enzyme of serotype M49 group A Streptococcus that hydrolyses N-linked glycans on IgG and α1-acid glycoprotein.
- Authors: Sjögren J, Struwe WB, Cosgrave EF, Rudd PM, Stervander M, Allhorn M, Hollands A, Nizet V, Collin M
- Issue date: 2013 Oct 1
- The structure of a glycoside hydrolase 29 family member from a rumen bacterium reveals unique, dual carbohydrate-binding domains.
- Authors: Summers EL, Moon CD, Atua R, Arcus VL
- Issue date: 2016 Oct 1
- Crystal structure of Streptococcus pyogenes EndoS, an immunomodulatory endoglycosidase specific for human IgG antibodies.
- Authors: Trastoy B, Lomino JV, Pierce BG, Carter LG, Günther S, Giddens JP, Snyder GA, Weiss TM, Weng Z, Wang LX, Sundberg EJ
- Issue date: 2014 May 6
- Liquid-liquid diffusion crystallization improves the X-ray diffraction of EndoS, an endo-β-N-acetylglucosaminidase from Streptococcus pyogenes with activity on human IgG.
- Authors: Trastoy B, Lomino JV, Wang LX, Sundberg EJ
- Issue date: 2013 Dec
- βγ-Crystallination Endows a Novel Bacterial Glycoside Hydrolase 64 with Ca<sup>2+</sup>-Dependent Activity Modulation.
- Authors: Krishnan B, Srivastava SS, Sankeshi V, Garg R, Srivastava S, Sankaranarayanan R, Sharma Y
- Issue date: 2019 Dec 1