Ligand binding energy and enzyme efficiency from reductions in protein dynamics

J Mol Biol. 2006 Jan 27;355(4):760-7. doi: 10.1016/j.jmb.2005.11.015. Epub 2005 Nov 22.

Abstract

Tetrameric rabbit muscle glyceraldehyde 3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) binds successively four molecules of its cofactor (NAD+) with affinities of ca 10(11) M(-1), 10(9) M(-1), 10(7) M(-1), and 10(5) M(-1). The reduction in the dynamics of the protein is greatest upon binding the first NAD+ molecule. Smaller reductions then occur upon binding the second and third NAD+ molecules, and the fourth NAD+ molecule binds without dynamic change. Reduction of the GAPDH dynamics, with consequent improvements in its internal bonding, can account for the increase in NAD+ binding affinity from 10(5) M(-1) to 10(11) M(-1). Evidence is provided that comparable fractions of the binding energy of other ligands, and of the catalytic efficiency of enzymes, may be derived in the same way.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalysis
  • Glyceraldehyde-3-Phosphate Dehydrogenases / chemistry*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
  • Ligands
  • Models, Biological
  • Muscles / chemistry
  • Muscles / metabolism
  • Oxidation-Reduction
  • Protein Binding
  • Rabbits
  • Thermodynamics

Substances

  • Ligands
  • Glyceraldehyde-3-Phosphate Dehydrogenases