NMR and modeling studies of protein-carbohydrate interactions: synthesis, three-dimensional structure, and recognition properties of a minimum hevein domain with binding affinity for chitooligosaccharides

Chembiochem. 2004 Sep 6;5(9):1245-55. doi: 10.1002/cbic.200400025.

Abstract

HEV32, a 32-residue, truncated hevein lacking eleven C-terminal amino acids, was synthesized by solid-phase methodology and correctly folded with three cysteine bridge pairs. The affinities of HEV32 for small chitin fragments--in the forms of N,N',N"-triacetylchitotriose ((GlcNAc)3) (millimolar) and N,N',N",N"',N"",N""'-hexaacetylchitohexaose ((GlcNAc)6) (micromolar)--as measured by NMR and fluorescence methods, are comparable with those of native hevein. The HEV32 ligand-binding process is enthalpy driven, while entropy opposes binding. The NMR structure of ligand-bound HEV32 in aqueous solution was determined to be highly similar to the NMR structure of ligand-bound hevein. Solvated molecular-dynamics simulations were performed in order to monitor the changes in side-chain conformation of the binding site of HEV32 and hevein upon interaction with ligands. The calculations suggest that the Trp21 side-chain orientation of HEV32 in the free form differs from that in the bound state; this agrees with fluorescence and thermodynamic data. HEV32 provides a simple molecular model for studying protein-carbohydrate interactions and for understanding the physiological relevance of small native hevein domains lacking C-terminal residues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / chemistry*
  • Amaranthus / chemistry
  • Amino Acid Sequence
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry*
  • Carbohydrate Sequence
  • Carbohydrates / chemistry*
  • Chromatography, High Pressure Liquid
  • Crystallography, X-Ray
  • Latex Hypersensitivity
  • Lectins / chemistry
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Oligosaccharides / chemistry*
  • Plant Lectins / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Proteins / chemistry*
  • Spectrometry, Fluorescence
  • Thermodynamics

Substances

  • Allergens
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Carbohydrates
  • Lectins
  • Ligands
  • Oligosaccharides
  • Plant Lectins
  • Proteins
  • hevein