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.

Identification of Novel and Potent Indole-Based Benzenesulfonamides as Selective Human Carbonic Anhydrase II Inhibitors: Design, Synthesis, In Vitro, and In Silico Studies

“…Carbonic anhydrases (CAs) are metalloenzymes found in all living things that are required for the conversion of CO 2 to bicarbonate and protons [ 1 ]. CAs observed in humans belong to the α-class (α-CA), and are classified into sixteen isoforms that vary in molecular characteristics, oligomeric structure, cellular localization, distribution in organs and tissues, expression levels, and kinetic properties [ 2 ].…”

Amine- and Amino Acid-Based Compounds as Carbonic Anhydrase Activators

“…In this context are the Carbonic Anhydrase (CA; EC 4.2.1.1) enzymes which are particularly efficient in speeding-up this equilibrium, thus allowing it in covering any biological need. The abundance of genetic families (i.e., eight and non-correlated to each other) and the multitude of isoforms expressed within some of them clearly reflects the remarkable physio/pathological value of such enzymes which are among the most striking examples of convergent evolution in biology [ 6 , 7 ]. According to the genetic branch, CAs are identified as α-, β-, γ-, δ-, ζ-, η-, θ-, and ι-classes.…”

“…However, the enzymes were found to be catalytically active without the metal ion, and a putative catalytic mechanism was proposed, with the hydroxyl groups of amino acidic residues (i.e., Thr106, Tyr124 and Ser199) involved in the deprotonation of the active site water [ 29 ]. It is unclear whether these metal-free CAs belong to a ι-CA subclass or whether all ι-CAs discovered so far do not need a metal cofactor for the catalytic cycle and the zinc or manganese ion required for the activity only has a structural function [ 7 ].…”

Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol, Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents, and Carbonic Anhydrases I, II, VII, IX, and XII Inhibitors

“…Inhibition of bacterial CAs leads to the inhibition of growth, growth defects, and makes bacteria vulnerable to host defense mechanisms [ 4 , 8 , 9 ]. Over the last few years, a number of articles describing the inhibition activity of clinically licensed or new sulfonamides against bacterial CAs presented in Vibrio cholerae [ 10 , 11 , 12 , 13 , 14 ], Mycobacterium tuberculosis [ 15 , 16 , 17 , 18 ], Burkholderia pseudomallei [ 19 ], Burkholderia territorii [ 7 , 20 ], Escherichia coli [ 21 , 22 ], and others, were published.…”