Structural insights into β-1,3-glucan cleavage by a glycoside hydrolase family

Nat Chem Biol. 2020 Aug;16(8):920-929. doi: 10.1038/s41589-020-0554-5. Epub 2020 May 25.

Abstract

The fundamental and assorted roles of β-1,3-glucans in nature are underpinned on diverse chemistry and molecular structures, demanding sophisticated and intricate enzymatic systems for their processing. In this work, the selectivity and modes of action of a glycoside hydrolase family active on β-1,3-glucans were systematically investigated combining sequence similarity network, phylogeny, X-ray crystallography, enzyme kinetics, mutagenesis and molecular dynamics. This family exhibits a minimalist and versatile (α/β)-barrel scaffold, which can harbor distinguishing exo or endo modes of action, including an ancillary-binding site for the anchoring of triple-helical β-1,3-glucans. The substrate binding occurs via a hydrophobic knuckle complementary to the canonical curved conformation of β-1,3-glucans or through a substrate conformational change imposed by the active-site topology of some fungal enzymes. Together, these findings expand our understanding of the enzymatic arsenal of bacteria and fungi for the breakdown and modification of β-1,3-glucans, which can be exploited for biotechnological applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence / genetics
  • Binding Sites / physiology
  • Catalytic Domain / physiology
  • Crystallography, X-Ray / methods
  • Glucan 1,3-beta-Glucosidase / chemistry*
  • Glucan 1,3-beta-Glucosidase / metabolism
  • Glucans / chemistry
  • Glycoside Hydrolases / chemistry*
  • Glycosides / chemistry
  • Models, Molecular
  • Substrate Specificity / physiology
  • beta-Glucans / chemistry*

Substances

  • Glucans
  • Glycosides
  • beta-Glucans
  • beta-1,3-glucan
  • Glycoside Hydrolases
  • Glucan 1,3-beta-Glucosidase