Structure, Function and Mechanism of N‐Glycan Processing Enzymes: <i>endo</i>‐α‐1,2‐Mannanase and <i>endo</i>‐α‐1,2‐Mannosidase

BURCHILL, Laura, MALES, Alexandra, KAUR, Arashdeep, DAVIES, Gideon J and WILLIAMS, Spencer J (2022). Structure, Function and Mechanism of N‐Glycan Processing Enzymes: <i>endo</i>‐α‐1,2‐Mannanase and <i>endo</i>‐α‐1,2‐Mannosidase. Israel Journal of Chemistry, 63 (1-2).

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Abstract

While most glycosidases that act on N-linked glycans remove a single sugar residue at a time, endo-α-1,2-mannosidases and endo-α-1,2-mannanases of glycoside hydrolase family GH99 cut within a chain and remove two or more sugar residues. They are stereochemically retaining enzymes that use an enzymatic mechanism involving an epoxide intermediate. Human endo-α-1,2-mannosidase (MANEA) trims glucosylated mannose residues; the endomannosidase pathway provides a glucosidase-independent pathway for glycoprotein maturation. Cell-active MANEA inhibitors alter N-glycan processing and reduce infectivity of dengue virus, demonstrating that MANEA has potential as a host-directed antiviral target. Sequence-related enzymes from gut Bacteroides spp. exhibit endo-α-1,2-mannosidase activity and are a fruitful test bed for structure-guided inhibitor development. The genes encoding the Bacteroides spp. enzymes sit within polysaccharide utilization loci and are preferential endo-α-1,2-mannanases.

Item Type:	Article
Uncontrolled Keywords:	03 Chemical Sciences; Chemical Physics; 34 Chemical sciences
Identification Number:	https://doi.org/10.1002/ijch.202200067
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	25 Sep 2023 12:01
Last Modified:	11 Oct 2023 11:30
URI:	https://shura.shu.ac.uk/id/eprint/32423

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