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An overview on the recently discovered iota-carbonic anhydrases.

ABSTRACT: Carbonic anhydrases (CAs, EC 4.2.1.1) have been studied for decades and have been classified as a superfamily of enzymes which includes, up to date, eight gene families or classes indicated with the Greek letters α, β, γ, δ, ζ, η, θ, ι. This versatile enzyme superfamily is involved in multiple physiological processes, catalysing a fundamental reaction for all living organisms, the reversible hydration of carbon dioxide to bicarbonate and a proton. Recently, the ι-CA (LCIP63) from the diatom Thalassiosira pseudonana and a bacterial ι-CA (BteCAι) identified in the genome of Burkholderia territorii were characterised. The recombinant BteCAι was observed to act as an excellent catalyst for the physiologic reaction. Very recently, the discovery of a novel ι-CAs (COG4337) in the eukaryotic microalga Bigelowiella natans and the cyanobacterium Anabaena sp. PCC7120 has brought to light an unexpected feature for this ancient superfamily: this ι-CAs was catalytically active without a metal ion cofactor, unlike the previous reported ι-CAs as well as all known CAs investigated so far. This review reports recent investigations on ι-CAs obtained in these last three years, highlighting their peculiar features, and hypothesising that possibly this new CA family shows catalytic activity without the need of metal ions.

SUBMITTER: Nocentini A

PROVIDER: S-EPMC8425729 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Polyamines and α-Carbonic Anhydrases.

Project description:Natural products represent a straightforward source for molecular structures bearing a vast array of chemical features and potentially useful for biomedical purposes. Recent examples of this type include the discovery of the coumarins and the polyamine natural products as atypical chemotypes for the inhibition of the metalloenzymes carbonic anhydrases (CAs; EC 4.2.2.1). CA enzymes are established pharmacological targets for important pathologies, which, among others, include glaucoma, hypoxic tumors, and central nervous system (CNS)-affecting diseases. Moreover, they are expressed in many bacteria, fungi and helminths which are the etiological agents of the majority of infectious diseases. In this context, natural products represent the ideal source of new and selective druggable CA modulators for biomedical purposes. Herein we report the state of the art on polyamines of natural origin as well as of synthetic derivatives as inhibitors of human CAs.

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Thermostable Carbonic Anhydrases in Biotechnological Applications.

Project description:Carbonic anhydrases are ubiquitous metallo-enzymes which catalyze the reversible hydration of carbon dioxide in bicarbonate ions and protons. Recent years have seen an increasing interest in the utilization of these enzymes in CO2 capture and storage processes. However, since this use is greatly limited by the harsh conditions required in these processes, the employment of thermostable enzymes, both those isolated by thermophilic organisms and those obtained by protein engineering techniques, represents an interesting possibility. In this review we will provide an extensive description of the thermostable carbonic anhydrases so far reported and the main processes in which these enzymes have found an application.

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α-Carbonic Anhydrases Possess Thioesterase Activity.

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Coumarins effectively inhibit bacterial α-carbonic anhydrases.

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Carbonic Anhydrases: Role in pH Control and Cancer.

Project description:The pH of the tumor microenvironment drives the metastatic phenotype and chemotherapeutic resistance of tumors. Understanding the mechanisms underlying this pH-dependent phenomenon will lead to improved drug delivery and allow the identification of new therapeutic targets. This includes an understanding of the role pH plays in primary tumor cells, and the regulatory factors that permit cancer cells to thrive. Over the last decade, carbonic anhydrases (CAs) have been shown to be important mediators of tumor cell pH by modulating the bicarbonate and proton concentrations for cell survival and proliferation. This has prompted an effort to inhibit specific CA isoforms, as an anti-cancer therapeutic strategy. Of the 12 active CA isoforms, two, CA IX and XII, have been considered anti-cancer targets. However, other CA isoforms also show similar activity and tissue distribution in cancers and have not been considered as therapeutic targets for cancer treatment. In this review, we consider all the CA isoforms and their possible role in tumors and their potential as targets for cancer therapy.

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Legionella pneumophila Carbonic Anhydrases: Underexplored Antibacterial Drug Targets.

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Role of carbonic anhydrases in skin wound healing.

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Bacterial carbonic anhydrases as drug targets: toward novel antibiotics?

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