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Special Issue "Carbonic Anhydrases: A Superfamily of Ubiquitous Enzymes 2.0"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 31 May 2021.

Special Issue Editor

Prof. Dr. Clemente Capasso
Guest Editor
Institute of Bioscience and Bioresources (IBBR), National Research Council, Via Pietro Castellino 111, 80131 Napoli, Italy
Interests: protein biochemistry, recombinant protein, heterologous expression, carbonic anhydrase, enzyme and protein purification, enzyme characterization, enzyme thermostability, cold-adapted enzymes
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Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous special issue "Carbonic Anhydrases: A Superfamily of Ubiquitous Enzymes".

The superfamily of carbonic anhydrases (CAs, EC 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+. Their crucial role is to equilibrate the reaction between three essential chemical species: CO2, bicarbonate (HCO3), and protons (H+). These chemical species are metabolites distributed throughout the fluids of all living organisms and are involved in a large number of physiologic and biosynthetic processes, such as respiration, photosynthesis, gluconeogenesis, lipogenesis, ureagenesis, carboxylation, and biochemical pathways involving pH homeostasis. Furthermore, processes such as secretion of electrolytes, calcification, bone resorption, transport of CO2 and bicarbonate are assisted by these enzymes. Up to date, the CA superfamily contains seven genetically distinct families (or classes), named α-, β-, γ-, δ-, ζ-, η-, and ɵ-CAs. The α-CAs were discovered in vertebrates, eubacteria, algae, and in the cytoplasm of green plants; the β-CAs were identified in eubacteria, algae, and in the chloroplasts of both mono- and dicotyledons; the γ-CAs were found mainly in Archaea and some eubacteria; the δ- and ζ-CAs are typical of the marine diatoms. The η- and q-CAs were recently discovered. The η-CA was recognized in the genome of the protozoa Plasmodia falciparum, while the q-CA was identified in the lumen of the pyrenoid-penetrating thylakoid of the unicellular alga Phaeodactylum tricornutum. From a phylogenetic viewpoint, the seven classes are an example of convergent evolution, since all classes show low sequence similarity and different folds and structures, while having a common CO2 hydratase activity, with the catalytically active species represented by a metal hydroxide derivative. These enzymes are also characterized by the presence of a large number of isoforms in most organisms investigated so far.

Drugs interfering with CAs activity have been clinically used for more than 70 years, most of them belonging to the sulfonamide class. 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); 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 in the therapy and diagnosis of cancer.  An emerging area is studying CAI as anti-infectives, i.e., as antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action, since it has been seen that the inhibition of pathogens’ CAs leads to growth impairment or growth defects in the host microorganisms.

The CA superfamily can bind molecules known as “activators” (CAA) through the middle-exit part of the active site. CAA are biogenic amines (histamine, serotonin, and catecholamines), amino acids, oligopeptides, or small proteins. CAAs enhance the catalytic constant (kcat) of the enzyme, with no effect on the KM. CAAs may have pharmacologic applications in the therapy of memory-related disorders, neurodegenerative diseases (Alzheimer’s disease), and genetic CA-deficiency syndromes.

Moreover, since most bacteria are incredibly abundant in environments that are hostile to all other forms of life, CAs from extremophiles are exciting candidates for industrial and medical applications, such as the post-combustion carbon-capture process and the realization of artificial lungs and biosensors. The ancient CAs can be considered as a biotechnological multitasking superfamily because the various CA classes are potentially able to both fight the increase of CO2 in the atmosphere produced by anthropogenic activities and ameliorate human health because of their biomedical applications.

This Special Issue is dedicated to all the important advances in the field of carbonic anhydrases, their inhibitors and activators, and their potential use in medical and biotechnological applications, since the CA superfamily represents a very promising target for the scientific community for its ubiquity 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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • Metalloenzymes
  • bacteria
  • pathogens
  • sulfonamides
  • inhibitors
  • activators
  • antiinfective agents
  • medicine
  • anticancer
  • neurodegenerative diseases
  • biomedical applications
  • biotechnology
  • carbon capture

Published Papers (1 paper)

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Open AccessArticle
Effect of Sulfonamides and Their Structurally Related Derivatives on the Activity of ι-Carbonic Anhydrase from Burkholderia territorii
Int. J. Mol. Sci. 2021, 22(2), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020571 - 08 Jan 2021
Carbonic anhydrases (CAs) are essential metalloenzymes in nature, catalyzing the carbon dioxide reversible hydration into bicarbonate and proton. In humans, breathing and many other critical physiological processes depend on this enzymatic activity. The CA superfamily function and inhibition in pathogenic bacteria has recently [...] Read more.
Carbonic anhydrases (CAs) are essential metalloenzymes in nature, catalyzing the carbon dioxide reversible hydration into bicarbonate and proton. In humans, breathing and many other critical physiological processes depend on this enzymatic activity. The CA superfamily function and inhibition in pathogenic bacteria has recently been the object of significant advances, being demonstrated to affect microbial survival/virulence. Targeting bacterial CAs may thus be a valid alternative to expand the pharmacological arsenal against the emergence of widespread antibiotic resistance. Here, we report an extensive study on the inhibition profile of the recently discovered ι-CA class present in some bacteria, including Burkholderia territorii, namely BteCAι, using substituted benzene-sulfonamides and clinically licensed sulfonamide-, sulfamate- and sulfamide-type drugs. The BteCAι inhibition profile showed: (i) several benzene-sulfonamides with an inhibition constant lower than 100 nM; (ii) a different behavior with respect to other α, β and γ-CAs; (iii) clinically used drugs having a micromolar affinity. This prototype study contributes to the initial recognition of compounds which efficiently and selectively inhibit a bacterial member of the ι-CA class, for which such a selective inhibition with respect to other protein isoforms present in the host is highly desired and may contribute to the development of novel antimicrobials. Full article
(This article belongs to the Special Issue Carbonic Anhydrases: A Superfamily of Ubiquitous Enzymes 2.0)
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