A Molecular View of Glycosylation and Glycation Effects on the Structure of Human Acetylcholinesterase

All the organisms react to distinct signals from the environment. Fast reactions to those signals dictate the difference between life and death. Signaling cascade is modulated, among other molecules, by proteins. One of the most efficient enzymes is the acetylcholinesterase (ache) that catalyzes the hydrolysis of acetylcholine to choline and acetate. It is found in multiple molecular forms that determinate its function and location over the body. Ache needs to be modified postraductionally (glycosylation) to be active; being refers to the enzymatic process that binds monosaccharides on asparagines residues of the protein structure (n-glycosilation). Aditionally, glucose may be incorporated on lysine residues to protein by an inespecific process (glycation).In this work, we present the results of molecular simulations of ache in solution with different levels of glycosylation and glycation. Glycosylation was probed on 3 positions and glycation on 3 structurally conserved positions and all lysine residues solvent exposed of ache. 100ns of molecular simulations were done with explicit solvent at 298 k and 1 atm. The effect of sugar binding on the side chain residues of the binding site is presented.Cesar, MP. acknowledges to conacyt and Uam-I for Postdoctoral funding and Aitzaloa and National Computer Centre (IPICYT) for computer time and to Eduardo Jardon Valadez for his help on the early stages of this work.