Simulations of lysozyme: internal motions and the reaction mechanism

EXS. 1996:75:111-41. doi: 10.1007/978-3-0348-9225-4_8.

Abstract

Simulations of lysozyme by molecular dynamics have greatly increased our understanding of this enzyme. It has been shown how the internal motions are related to the structural elements (helices, sheets and loops) of the molecule. Comparisons of the motions in the free and substrate-bound form reveal that most are similar but that there are significant differences. Comparisons of the theoretical results with X-ray and nuclear magnetic resource data show good agreement. The hinge-bending motion, which opens and closes the binding site cleft between the two domains, is correlated with substrate binding. From analysis of simulations with bound substrate, an alternative mechanism for oligoglycoside hydrolysis was proposed. It involves cleavage of an endocyclic C-O bond, instead of the exocyclic cleavage proposed in the standard mechanism. Both mechanisms have been demonstrated in solution, but it is still unclear which is prevalent in lysozyme.

Publication types

  • Review

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Crystallography, X-Ray
  • Enzyme Inhibitors / metabolism
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Muramidase / chemistry*
  • Muramidase / metabolism*
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Thermodynamics

Substances

  • Enzyme Inhibitors
  • Oligosaccharides
  • Muramidase