Binding thermodynamics of the transition state analogue coformycin and of the ground state analogue 1-deazaadenosine to bovine adenosine deaminase

J Enzyme Inhib. 2001;16(3):217-32. doi: 10.1080/14756360109162370.

Abstract

Binding of the transition state analogue coformycin and the ground state analogue 1-deaazadenosine to bovine adenosine deaminase have been thermodynamically characterized. The heat capacity changes for coformycin and 1-deazaadenosine binding are -4.7 +/- 0.8 kJ/mole-K and -1.2 +/- 0.1 kJ/mole-K, respectively. Since the predominant source of heat capacity change in enzyme interactions are changes in the extent of exposure of nonpolar amino acid side chains to the aqueous environment and the hydrophobic effect is the predominant factor in native structure stabilization, we propose that the binding of either class of ligand is associated with a stabilizing enzyme conformational change with coformycin producing the far greater effect. Analysis of the T dependence of the second order rate constant for formation of the enzyme/coformycin complex further reveals that the conformational change is not rate limiting. We propose that the enzyme may facilitate catalysis via the formation of a stabilizing conformation at the reaction transition state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / chemistry
  • Adenosine Deaminase / metabolism*
  • Adenosine Deaminase Inhibitors
  • Animals
  • Binding Sites
  • Cattle
  • Coformycin / chemistry
  • Coformycin / metabolism*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Mathematics
  • Molecular Structure
  • Protein Binding
  • Protein Structure, Tertiary*
  • Protein Synthesis Inhibitors / chemistry
  • Protein Synthesis Inhibitors / metabolism
  • Temperature
  • Thermodynamics
  • Tubercidin / chemistry
  • Tubercidin / metabolism*

Substances

  • Adenosine Deaminase Inhibitors
  • Enzyme Inhibitors
  • Protein Synthesis Inhibitors
  • Coformycin
  • 1-deazaadenosine
  • Adenosine Deaminase
  • Tubercidin