Journal Article

Mechanism of cooperative N-glycan processing by the multi-modular endoglycosidase EndoE

Sultana, Nazneen, Ordóñez, Izaskun, Diz-Vallenilla, Asier, Du, Jonathan J., Sundberg, Eric J., Trastoy, Beatriz, Donahue, Thomas Connor, Wang, Lai-Xi, Guerin, Marcelo E., Huynh, Chau G., García-Alija, Mikel, Li, Chao, Moraleda-Montoya, Alicia

2022

Overview

Bacteria produce a remarkably diverse range of glycoside hydrolases to metabolize glycans from the environment as a primary source of nutrients, and to promote the colonization and infection of a host. Here we focus on EndoE, a multi-modular glycoside hydrolase secreted by Enterococcus faecalis , one of the leading causes of healthcare-associated infections. We provide X-ray crystal structures of EndoE, which show an architecture composed of four domains, including GH18 and GH20 glycoside hydrolases connected by two consecutive three α-helical bundles. We determine that the GH20 domain is an exo-β-1,2- N -acetylglucosaminidase, whereas the GH18 domain is an endo-β-1,4- N -acetylglucosaminidase that exclusively processes the central core of complex-type or high-mannose-type N -glycans. Both glycoside hydrolase domains act in a concerted manner to process diverse N -glycans on glycoproteins, including therapeutic IgG antibodies. EndoE combines two enzyme domains with distinct functions and glycan specificities to play a dual role in glycan metabolism and immune evasion. EndoE is a multi-domain glycoside hydrolase of the human pathogen Enterococcus faecalis . Here, the authors present crystal structures of EndoE and provide biochemical insights into the molecular basis of EndoE’s substrate specificity and catalytic mechanism.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 101/58 / 631/326/41/2536 / 631/45/173 / 631/45/221 / 631/535/1266 / 82/16 / 82/29 / 82/80 / 82/83 / Acetylglucosaminidase - metabolism / Antibodies / Bacteria / Biochemistry / Carbohydrates / Crystal structure / Domains / Enterococcus faecalis / Enterococcus faecalis - metabolism / Enzymes / Glycan / Glycoproteins / Glycosidases / Glycoside hydrolase / Glycoside Hydrolases - metabolism / Glycosides / Humanities and Social Sciences / Hydrolase / Immunoglobulin G / Infections / Laboratories / Mannose / Mannose - metabolism / Microprocessors / multidisciplinary / N-Acetylglucosaminidase / N-glycans / Nutrients / Pathogens / Polysaccharides / Polysaccharides - metabolism / Science / Science (multidisciplinary) / Substrate specificity / Substrates