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Atomic Absorbance Spectroscopy to Measure Intracellular Zinc Pools in Mammalian Cells
Published on: May 16, 2019
The carboxylate shift in zinc enzymes: a computational study
Sérgio F Sousa1, Pedro A Fernandes, Maria João Ramos
1REQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal.
Journal of the American Chemical Society
|February 1, 2007
Summary
This study reveals how zinc enzymes utilize carboxylate shifts for catalysis. Specific amino acid combinations in zinc
Area of Science:
- Biochemistry and enzymology
- Bioinorganic chemistry
- Computational chemistry
Background:
- Zinc is a crucial transition metal in biological catalysis, present in all enzyme classes.
- Its unique properties, including flexible coordination and Lewis acid activity, are vital for enzyme function.
- Mononuclear zinc enzymes employ various mechanisms, including the carboxylate shift, to facilitate catalytic processes.
Purpose of the Study:
- To investigate the significance of the carboxylate shift mechanism in mononuclear zinc enzymes.
- To elucidate the relationship between zinc coordination sphere characteristics and the carboxylate shift.
- To identify amino acid residues that optimize zinc enzyme activity through this mechanism.
Main Methods:
- Utilized density functional theory (DFT) calculations, specifically B3LYP.
- Analyzed the coordination geometry of zinc ions in mononuclear enzymes.
- Examined the influence of carboxylate ligand coordination modes (mono- to bidentate) on catalytic activity.
Main Results:
- Identified key patterns linking zinc coordination sphere properties to the occurrence of carboxylate shifts.
- Quantified the energy stabilization provided by the carboxylate shift mechanism.
- Determined that a specific coordination sphere (carboxylate, cysteine, histidine) is optimal for fast ligand exchange.
Conclusions:
- The carboxylate shift is an important mechanistic phenomenon in zinc enzyme catalysis.
- The intrinsic properties of the zinc coordination sphere dictate the feasibility and energetic favorability of carboxylate shifts.
- A zinc coordination sphere involving aspartate/glutamate, cysteine, and histidine offers the most favorable conditions for rapid ligand exchange, enhancing catalytic efficiency.
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