PMID- 16325850 OWN - NLM STAT- MEDLINE DCOM- 20060227 LR - 20061115 IS - 0022-2836 (Print) IS - 0022-2836 (Linking) VI - 355 IP - 4 DP - 2006 Jan 27 TI - Ligand binding energy and enzyme efficiency from reductions in protein dynamics. PG - 760-7 AB - 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. FAU - Williams, Dudley H AU - Williams DH AD - Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, UK. dhw1@cam.ac.uk FAU - Zhou, Min AU - Zhou M FAU - Stephens, Elaine AU - Stephens E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051122 PL - Netherlands TA - J Mol Biol JT - Journal of molecular biology JID - 2985088R RN - 0 (Ligands) RN - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases) SB - IM MH - Animals MH - Catalysis MH - Glyceraldehyde-3-Phosphate Dehydrogenases/*chemistry/*metabolism MH - Ligands MH - Models, Biological MH - Muscles/chemistry/metabolism MH - Oxidation-Reduction MH - Protein Binding MH - Rabbits MH - Thermodynamics EDAT- 2005/12/06 09:00 MHDA- 2006/02/28 09:00 CRDT- 2005/12/06 09:00 PHST- 2005/09/02 00:00 [received] PHST- 2005/10/20 00:00 [revised] PHST- 2005/11/05 00:00 [accepted] PHST- 2005/12/06 09:00 [pubmed] PHST- 2006/02/28 09:00 [medline] PHST- 2005/12/06 09:00 [entrez] AID - S0022-2836(05)01401-4 [pii] AID - 10.1016/j.jmb.2005.11.015 [doi] PST - ppublish SO - J Mol Biol. 2006 Jan 27;355(4):760-7. doi: 10.1016/j.jmb.2005.11.015. Epub 2005 Nov 22.