Crystal structure of a class I alpha1,2-mannosidase involved in N-glycan processing and endoplasmic reticulum quality control

EMBO J. 2000 Feb 15;19(4):581-8. doi: 10.1093/emboj/19.4.581.


Mannose trimming is not only essential for N-glycan maturation in mammalian cells but also triggers degradation of misfolded glycoproteins. The crystal structure of the class I alpha1, 2-mannosidase that trims Man(9)GlcNAc(2) to Man(8)GlcNAc(2 )isomer B in the endoplasmic reticulum of Saccharomyces cerevisiae reveals a novel (alphaalpha)(7)-barrel in which an N-glycan from one molecule extends into the barrel of an adjacent molecule, interacting with the essential acidic residues and calcium ion. The observed protein-carbohydrate interactions provide the first insight into the catalytic mechanism and specificity of this eukaryotic enzyme family and may be used to design inhibitors that prevent degradation of misfolded glycoproteins in genetic diseases.

Publication types

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

MeSH terms

  • Carbohydrate Sequence
  • Crystallography, X-Ray
  • Endoplasmic Reticulum / metabolism
  • Mannosidases / chemistry*
  • Mannosidases / genetics
  • Mannosidases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism
  • Protein Conformation
  • Quality Control
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Substrate Specificity


  • Oligosaccharides
  • Polysaccharides
  • Recombinant Proteins
  • Mannosidases
  • mannosyl-oligosaccharide 1,2-alpha-mannosidase

Associated data

  • PDB/1DL2