title: A QM/MM MD study of the pH-dependent ring-opening catalysis and lid motif flexibility in glucosamine 6-phosphate deaminase.
abstract: The glucosamine 6-phosphate deaminase (NagB), which catalyzes the conversion of D-glucosamine 6-phosphate (GlcN6P) into d-fructose 6-phosphate (F6P) and ammonia, determines the final metabolic fate of N-acetylglucosamine (GlcNAc). Here using state-of-the-art ab initio QM/MM MD simulations, we have explored the plausible mechanisms for the enzymatic ring-opening of GlcN6P in the basic environment. Two different proton-shuttle mechanisms have been proposed. Calculations show that the protonated state of the amino group in the substrate dominates the concerted and stepwise catalytic pathways and a catalytic triad plays an important role in mediating the proton transfer and the resulting ring-opening process. The free energy barrier for the rate-determining step in the low-energy stepwise reaction is 17.9 kcal mol(-1). In acidic solution, the lid motif prefers a closed state while it always stays in the open state in basic solution upon substrate binding, which is basically dominated by the protonated state of the residue His145.
authors: State Key Laboratory of Physical Chemistry of Solid Surfaces and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China. zxcao@xmu.edu.cn.
authors: Yuan
authors: Y
authors: Zhao
authors: Nanhao
authors: N
authors: Chen
authors: Ruibo
authors: R
authors: Wu
authors: Zexing
authors: Z
authors: Cao
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000737:chemistry* / Q000648:ultrastructure*; D020816:Amino Acid Motifs; D002384:Catalysis; D003198:Computer Simulation; D004789:Enzyme Activation; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D011789:Quantum Theory
chemical_list: C020582:glucosamine-6-phosphate isomerase; D019747:Aldose-Ketose Isomerases