Changes in the free energy profile of glutamate mutase imparted by the mutation of an active site arginine residue to lysine

Arch Biochem Biophys. 2007 May 15;461(2):194-9. doi: 10.1016/j.abb.2007.01.010. Epub 2007 Jan 31.

Abstract

Arginine 100 plays an important role in substrate recognition in adenosylcobalamin-dependent glutamate mutase. We have examined how the mutation of this residue to lysine affects the partitioning of tritium, incorporated at the exchangeable position of the coenzyme, between substrate and product. We find that partitioning of tritium back to the substrate predominates in the mutant enzyme, regardless of whether the reaction is run in the forward or reverse direction. This contrasts with the behavior of the wild-type enzyme in which tritium partitions equally between substrate and product, independent of the direction of the reaction. From this we conclude that the mutation significantly impairs the ability of the enzyme to catalyze the rearrangement of substrate radical to product radical. The results illustrate the importance of electrostatic interactions in stabilizing free radical intermediates in this class of enzymes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution*
  • Arginine / genetics
  • Arginine / metabolism*
  • Binding Sites / genetics
  • Intramolecular Transferases / genetics
  • Intramolecular Transferases / metabolism*
  • Kinetics
  • Lysine / genetics
  • Lysine / metabolism*
  • Substrate Specificity / genetics
  • Thermodynamics*

Substances

  • Arginine
  • Intramolecular Transferases
  • methylaspartate mutase
  • Lysine