title: L-alpha-glycerophosphate binding to bovine gamma-crystallin: a potential link between metabolism and supramolecular order.
abstract: The highly selective nature of protein-ligand interactions provides a sensitive mechanism for the modulation of cellular activity by proteins. In the eye lens the supramolecular order of the lens crystallins, which is expected to be susceptible to protein electrostatic charge, in part defines transparency. The binding of charged ligands to proteins is one way of achieving an alteration in protein electrostatic charge. Evidence is presented that L-alpha-glycerophosphate, a major phosphorus metabolite of eye lens metabolism, binds to the globular protein, gamma-crystallin with moderately high affinity and in a positive cooperative manner. The following binding parameters were obtained from equilibrium measurements: minimum number of binding sites, n = 2; Kassoc = 6.2 +/- 0.5 x 10(3) M-1; cooperativity parameter, alpha H = 1.9 +/- 0.1. Interactive computer graphics display techniques were used to locate putative ligand binding sites, and in turn, to identify the possible molecular interactions responsible for the binding of ligand to protein at one of the sites. One putative binding site was located in the cleft between the two domains of gamma II-crystallin. Arginyl residues 79 and 147 are involved in ligand binding as are the peptide carbonyl oxygens of residues Tyrosyl-50 and Aspartyl-156. Five hydrogen bonds between the ligand and the protein structure are predicted for the binding of L-alpha-glycerophosphate, whereas only 3 occur for the binding of the "unnatural" D-enantiomorph. Modulation of both lens protein supramolecular organization and lens metabolism is predicted to be a consequence of L-alpha-glycerophosphate binding to gamma-crystallin in the lens.
authors: Department of Physiology, UMD-New Jersey Medical School, Newark 07103.
authors: P N
authors: PN
authors: Farnsworth
authors: B
authors: B
authors: Groth-Vasselli
authors: R L
authors: RL
authors: Mathur
authors: J C
authors: JC
authors: Macdonald
authors: T
authors: T
authors: Schleich
mesh_terms: D000818:Animals; D002417:Cattle; D003196:Computer Graphics; D003459:Crystallins / Q000378:metabolism*; D004563:Electrochemistry; D005994:Glycerophosphates / Q000378:metabolism*; D007908:Lens, Crystalline / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding
chemical_list: D003459:Crystallins; D005994:Glycerophosphates; D008024:Ligands; C029620:alpha-glycerophosphoric acid