A QM/MM MD study of the pH-dependent ring-opening catalysis and lid motif flexibility in glucosamine 6-phosphate deaminase

Literature Information

Publication Date 2014-07-15
DOI 10.1039/C4CP01609B
Impact Factor 3.676
Authors

Yuan Zhao, Nanhao Chen, Ruibo Wu, Zexing Cao


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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.

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Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics
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Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.

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