Ligand binding energy and enzyme efficiency from reductions in protein dynamics.
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.
Williams
Dudley H
DH
Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, UK. dhw1@cam.ac.uk
Zhou
Min
M
Stephens
Elaine
E
D000818:Animals; D002384:Catalysis; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008954:Models, Biological; D009132:Muscles / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D011817:Rabbits; D013816:Thermodynamics
D008024:Ligands; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases