Structure and ligand binding of carbohydrate-binding module CsCBM6-3 reveals similarities with fucose-specific lectins and "galactose-binding" domains

J Mol Biol. 2003 Mar 28;327(3):659-69. doi: 10.1016/s0022-2836(03)00152-9.

Abstract

Carbohydrate-binding polypeptides, including carbohydrate-binding modules (CBMs) from polysaccharidases, and lectins, are widespread in nature. Whilst CBMs are classically considered distinct from lectins, in that they are found appended to polysaccharide-degrading enzymes, this distinction is blurring. The crystal structure of CsCBM6-3, a "sequence-family 6" CBM in a xylanase from Clostridium stercorarium, at 2.3 A reveals a similar, all beta-sheet fold to that from MvX56, a module found in a family 33 glycoside hydrolase sialidase from Micromonospora viridifaciens, and the lectin AAA from Anguilla anguilla. Sequence analysis leads to the classification of MvX56 and AAA into a family distinct from that containing CsCBM6-3. Whilst these polypeptides are similar in structure they have quite different carbohydrate-binding specificities. AAA is known to bind fucose; CsCBM6-3 binds cellulose, xylan and other beta-glucans. Here we demonstrate that MvX56 binds galactose, lactose and sialic acid. Crystal structures of CsCBM6-3 in complex with xylotriose, cellobiose, and laminaribiose, 2.0 A, 1.35 A, and 1.0 A resolution, respectively, reveal that the binding site of CsCBM6-3 resides on the same polypeptide face as for MvX56 and AAA. Subtle differences in the ligand-binding surface give rise to the different specificities and biological activities, further blurring the distinction between classical lectins and CBMs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrates / chemistry
  • Cellobiose / chemistry
  • Clostridium / enzymology
  • Crystallography, X-Ray
  • DNA / metabolism
  • Disaccharides / chemistry
  • Electrons
  • Fucose / chemistry*
  • Kinetics
  • Lectins / chemistry*
  • Ligands
  • Models, Chemical
  • Models, Molecular
  • Oligosaccharides / chemistry
  • Polysaccharides / chemistry
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Thermodynamics
  • Xylan Endo-1,3-beta-Xylosidase
  • Xylosidases / chemistry

Substances

  • Carbohydrates
  • Disaccharides
  • Lectins
  • Ligands
  • Oligosaccharides
  • Polysaccharides
  • laminaribiose
  • Cellobiose
  • Fucose
  • DNA
  • Xylosidases
  • Xylan Endo-1,3-beta-Xylosidase