Structure, Function and Mechanism of N‐Glycan Processing Enzymes: endo‐α‐1, 2‐Mannanase and endo‐α‐1, 2‐Mannosidase. Issue 1 (19th October 2022)

• Record Type: Journal Article
• Authors: Burchill, Laura; Males, Alexandra; Kaur, Arashdeep; Davies, Gideon J.; Williams, Spencer J.
• Other Names: Kramer Jessica R. guestEditor.; Pratt Matthew R. guestEditor.; Schumann Benjamin guestEditor.
• Is Part Of: Israel journal of chemistry. Volume 63:Issue 1/2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-19
• Subjects: carbohydrates -- glycoproteins -- endomannosidase pathway -- glycosidase -- iminosugar; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/ijch.202200067
• Languages: English
• ISSNs: 0021-2148

Abstract

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. Abstract :