From Microbes to Humans: Unveiling the Dynamic World of Carbonic Anhydrases (CAs)

Dear Colleagues,

The superfamily of carbonic anhydrases (CAs, EC 4.2.1.1) represents a group of ubiquitous proteins, which catalyze the physiologically important hydration–dehydration reaction of carbon dioxide to bicarbonate and protons: CO₂ + H₂O ⇄ HCO₃⁻ + H⁺.

Since CO₂, HCO₃⁻, and H⁺ are metabolites distributed throughout the fluids of all living organisms, CAs are involved in a large number of physiologic and biosynthetic processes, such as respiration, photosynthesis, gluconeogenesis, lipogenesis, ureagenesis, carboxylation, secretion of electrolytes, pH homeostasis, calcification, bone resorption, and transport of CO₂ and HCO₃⁻. To date, the CA superfamily contains eight genetically distinct families (or classes), named α-, β-, γ-, δ-, ζ-, η-, θ-, and ι-CAs. The distribution of the CA classes is somewhat assorted in most investigated organisms, and except for mammals which encode only for α-CAs, most of them possess multiple representatives of two or even more genetic families. In plants, α- and β-CAs have been recognized.

In Bacteria, Archaea, and cyanobacteria, α-, β-, γ-, and ι-CA classes are present. Marine diatoms encode for α-, δ-, ζ-, θ- and ι-CAs. In protozoa, α-, β-, and η-CAs have been detected. In the fungal kingdom, the typical class is represented by β-CAs, and most fungi encode at least one β-CA. In filamentous ascomycetes, it is also possible to find genes encoding for α-CAs. From a phylogenetic viewpoint, the eight CA classes are an example of convergent evolution: all CA classes show low sequence similarity and different folds and structures, having a common CO₂ hydratase activity.

Many CA inhibitors (CAI) exist, which could be classified as inhibitors binding the metal ion (anion, sulfonamides and their bioisosteres, dithiocarbamates, xanthates), inhibitors anchoring to the water molecule/hydroxide ion coordinated to the metal (phenols, polyamines, thioxocoumarins, sulfocumarins), and inhibitors occluding the active site entrance (coumarins and their isosteres); inhibitors binding outside of the active site.

Inhibition of CAs has many pharmacologic applications, such as against glaucoma, convulsions, obesity, and cancer. Today, an emerging area is studying CAI as anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents.

This Special Issue is dedicated to all the fundamental advances in the field of carbonic anhydrases since the CA superfamily represents a very promising target for the scientific community for its ubiquitous and crucial role in many physiologic and pathologic processes.

Original papers, reviews articles, and perspectives from experts in the field are welcome.

Prof. Dr. Clemente Capasso
Guest Editor

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• metalloenzymes
• bacteria
• pathogens
• sulfonamides
• inhibitors
• activators
• anti-infective agents
• medicine
• anticancer
• neurodegenerative diseases
• biomedical applications
• biotechnology