Function and Mechanism of Zinc Metalloenzymes

• Published in: The Journal of nutrition Vol. 130; no. 5; pp. 1437S - 1446S
• Main Authors: McCall, Keith A., Huang, Chih-chin, Fierke, Carol A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.05.2000; American Society for Nutritional Sciences; American Institute of Nutrition
• Subjects: Analytical, structural and metabolic biochemistry; anhydrase; Animals; Binding Sites; Biological and medical sciences; carbonic; Carbonic Anhydrases - metabolism; Carbonic Anhydrases - physiology; Catalysis; Enzymes; Enzymes - metabolism; Enzymes - physiology; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Ligands; metalloenzyme; Miscellaneous; Molecular Structure; Structure-Activity Relationship; Zinc; Zinc - chemistry; Zinc - metabolism; Zinc - physiology; zinc-binding sites; carbonic; zinc; metalloenzyme; zinc-binding sites; CA; anhydrase; Binding site; Metal; Review; Mechanism of action; Metalloenzyme; Inorganic element; Zinc
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/130.5.1437S

Zinc is required for the activity of > 300 enzymes, covering all six classes of enzymes. Zinc binding sites in proteins are often distorted tetrahedral or trigonal bipyramidal geometry, made up of the sulfur of cysteine, the nitrogen of histidine or the oxygen of aspartate and glutamate, or a combination. Zinc in proteins can either participate directly in chemical catalysis or be important for maintaining protein structure and stability. In all catalytic sites, the zinc ion functions as a Lewis acid. Researchers in our laboratory are dissecting the determinants of molecular recognition and catalysis in the zinc-binding site of carbonic anhydrase. These studies demonstrate that the chemical nature of the direct ligands and the structure of the surrounding hydrogen bond network are crucial for both the activity of carbonic anhydrase and the metal ion affinity of the zinc-binding site. An understanding of naturally occurring zinc-binding sites will aid in creating de novo zinc-binding proteins and in designing new metal sites in existing proteins for novel purposes such as to serve as metal ion biosensors. J. Nutr. 130: 1437S—1446S, 2000.