Factors governing when a metal-bound water is deprotonated in proteins

Literature Information

Publication Date 2018-11-05
DOI 10.1039/C8CP04776F
Impact Factor 3.676
Authors

Cédric Grauffel


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Abstract

Understanding when a metal-bound water molecule in a protein is deprotonated is important as this affects the charge distribution in the metal-binding/enzyme active site and thus their interactions, the enzyme mechanism, and inhibitor design. The protonation state of the metal-bound water molecule at a given pH depends on its pKa value, which in turn depends on the properties of the cation, its ligands, and the protein environment. Here, we reveal how and the extent to which (i) the first-shell composition (type, charge, and number of ligands), (ii) the metal site's immediate surroundings (first-shell⋯second-shell hydrogen-bonding interactions, metal–ligand distance constraints, and ligand-binding mode) and (iii) the protein architecture and coupled solvent interactions (long-range electrostatic interactions and solvent exposure of the site) affect the Zn2+-bound water pKa. The results, which are consistent with available experimental pKa values of Zn2+-bound water, provide guidelines to predict when Zn2+-bound water would likely be deprotonated at physiological pH.

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Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics
CiteScore: 5.5
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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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