Ligand binding energy and enzyme efficiency from reductions in protein dynamics |
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Authors: | Williams Dudley H Zhou Min Stephens Elaine |
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Affiliation: | Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, UK. dhw1@cam.ac.uk |
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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. |
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Keywords: | enzyme catalysis cooperativity non-covalent interactions binding energy |
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