Analysis of the structure and substrate scope of chitooligosaccharide oxidase reveals high affinity for C2-modified glucosamines

Simone Savino, Sonja Jensen, Anke Terwisscha van Scheltinga, Marco W Fraaije

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
74 Downloads (Pure)

Abstract

Chitooligosaccharide oxidase (ChitO) is a fungal carbohydrate oxidase containing a bicovalently bound FAD cofactor. The enzyme is known to catalyse the oxidation of chitooligosaccharides, oligomers of N-acetylated glucosamines derived from chitin degradation. In this study, the unique substrate acceptance was explored by testing a range of N-acetyl-D-glucosamine derivatives, revealing that ChitO preferentially accepts carbohydrates with a hydrophobic group attached to C2. The enzyme also accepts streptozotocin, a natural product used to treat tumours. Elucidation of the crystal structure provides an explanation for the high affinity towards C2-decorated glucosamines: the active site has a secondary binding pocket that accommodates groups attached at C2. Docking simulations are fully in line with the observed substrate preference. This work expands the knowledge on this versatile enzyme.

Original languageEnglish
Pages (from-to)2819-2828
Number of pages10
JournalFEBS Letters
Volume594
Issue number17
Early online date3-Jun-2020
DOIs
Publication statusPublished - 1-Sep-2020

Keywords

  • chitooligosaccharides
  • covalent flavin
  • crystal structure
  • glucosamine
  • oxidation

Cite this