A wheel invented three times. The molecular structures of the three carbonic anhydrases.
Ontology highlight
ABSTRACT:
SUBMITTER: Liljas A
PROVIDER: S-EPMC1083691 | biostudies-literature | 2000 Jul
REPOSITORIES: biostudies-literature
Publications
A wheel invented three times. The molecular structures of the three carbonic anhydrases.
EMBO reports 20000701 1
Similar Datasets
Project description:Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the interconversion of CO2 and HCO3- and are ubiquitous in nature. Higher plants contain three evolutionarily distinct CA families, αCAs, βCAs, and γCAs, where each family is represented by multiple isoforms in all species. Alternative splicing of CA transcripts appears common; consequently, the number of functional CA isoforms in a species may exceed the number of genes. CAs are expressed in numerous plant tissues and in different cellular locations. The most prevalent CAs are those in the chloroplast, cytosol, and mitochondria. This diversity in location is paralleled in the many physiological and biochemical roles that CAs play in plants. In this review, the number and types of CAs in C3, C4, and crassulacean acid metabolism (CAM) plants are considered, and the roles of the α and γCAs are briefly discussed. The remainder of the review focuses on plant βCAs and includes the identification of homologs between species using phylogenetic approaches, a consideration of the inter- and intracellular localization of the proteins, along with the evidence for alternative splice forms. Current understanding of βCA tissue-specific expression patterns and what controls them are reviewed, and the physiological roles for which βCAs have been implicated are presented.
| S-EPMC5226100 | biostudies-literature
Project description:Carbonic anhydrases (CA) belong to the family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate. In the present work, we characterized the cDNAs of four Paracoccidioides CAs (CA1, CA2, CA3, and CA4). In the presence of CO2, there was not a significant increase in fungal ca1, ca2 and ca4 gene expression. The ca1 transcript was induced during the mycelium-to-yeast transition, while ca2 and ca4 gene expression was much higher in yeast cells, when compared to mycelium and mycelium-to-yeast transition. The ca1 transcript was induced in yeast cells recovered directly from liver and spleen of infected mice, while transcripts for ca2 and ca4 were down-regulated. Recombinant CA1 (rCA1) and CA4 (rCA4), with 33 kDa and 32 kDa respectively, were obtained from bacteria. The enzymes rCA1 (?-class) and rCA4 (?-class) were characterized regarding pH, temperature, ions and amino acids addition influence. Both enzymes were stable at pHs 7.5-8.5 and temperatures of 30-35 °C. The enzymes were dramatically inhibited by Hg+2 and activated by Zn+2, while only rCA4 was stimulated by Fe2+. Among the amino acids tested (all in L configuration), arginine, lysine, tryptophan and histidine enhanced residual activity of rCA1 and rCA4.
| S-EPMC5004831 | biostudies-literature
Project description:Acipimox, a nicotinic acid derivative in clinical use for the treatment of hyperlipidaemia, incorporates a free carboxylic acid and an N-oxide moiety, functionalities known to interact with the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and inhibit its activity. Herein we report that acipimox acts as a low micromolar CA inhibitor (CAI) against most human (h) isoforms possessing catalytic activity, hCA I - XIV. By using computational techniques (docking and molecular dynamics simulations), we propose that acipimox coordinates through its carboxylate group to the zinc ion from the enzyme active site cavity, whereas the N-oxide group is hydrogen-bonded to the proton shuttle His residue in some isoforms (hCA I) or to active site Thr or Gln residues in other isoforms (hCA II, III, IV, VII, etc). As some CA isoforms are involved in lipogenesis, these data may be useful for the design of more effective CAIs with antiobesity activity.
| S-EPMC8843171 | biostudies-literature
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.
| S-EPMC6273118 | biostudies-literature
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.
| S-EPMC4519908 | biostudies-literature
Project description:The α-carbonic anhydrases (CAs, EC 4.2.1.1) show catalytic versatility acting as esterases with carboxylic, sulfonic, and phosphate esters. Here we prove by kinetic, spectroscopic, and MS studies that they also possess thioesterase activity with a dithiocarbamate ester as a substrate (PhSO2NHCSSMe). Its CA-mediated hydrolysis leads to benzenesulfonamide, methyl mercaptan, and COS. The CA thioesterase activity may be useful for designing prodrug enzyme inhibitors, whereas some CA isoforms may use this activity for modulating physiologic/pathologic processes, which are possibly amenable to drug discovery of agents with multiple mechanisms of action.
| S-EPMC4360143 | biostudies-literature
Project description:During recent decades, zebrafish (Danio rerio) have become one of the most important model organisms in which to study different physiological and biological phenomena. The research field of carbonic anhydrases (CAs) and carbonic anhydrase related proteins (CARPs) is not an exception to this. The best-known function of CAs is the regulation of acid-base balance. However, studies performed with zebrafish, among others, have revealed important roles for these proteins in many other physiological processes, some of which had not yet been predicted in the light of previous studies and suggestions. Examples include roles in zebrafish pigmentation as well as motor coordination. Disruption of the function of these proteins may generate lethal outcomes. In this review, we summarize the current knowledge of CA-related studies performed in zebrafish from 1993-2021 that was obtained from PubMed search.
| S-EPMC9032886 | biostudies-literature
Project description:Coumarins are known to act as prodrug inhibitors of mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) but they were not yet investigated for the inhibition of bacterial α-CAs. Here we demonstrate that such enzymes from the bacterial pathogens Neisseria gonorrhoeae (NgCAα) and Vibrio cholerae (VchCAα) are inhibited by a panel of simple coumarins incorporating hydroxyl, amino, ketone or carboxylic acid ester moieties in various positions of the ring system. The nature and the position of the substituents in the coumarin ring were the factors which strongly influenced inhibitory efficacy. NgCAα was inhibited with KIs in the range of 28.6-469.5 µM, whereas VchCAα with KIs in the range of 39.8-438.7 µM. The two human (h)CA isoforms included for comparison reason in the study, hCA I and II, were less prone to inhibition by these compounds, with KIs of 137-948.9 µM for hCA I and of 296.5-961.2 µM for hCA II, respectively. These findings are relevant for discovering coumarin bacterial CA inhibitors with selectivity for the bacterial over human isoform, with potential applications as novel antibacterial agents.
| S-EPMC8741243 | biostudies-literature
Project description:The atomic-resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors are reported. Each inhibitor contains a benzenesulfonamide prong and a cupric iminodiacetate (IDA-Cu(2+)) prong separated by linkers of different lengths and compositions. The ionized NH(-) group of each benzenesulfonamide coordinates to the active site Zn(2+) ion; the IDA-Cu(2+) prong of the tightest-binding inhibitor, BR30, binds to H64 of CAII and H200 of CAI. This work provides the first evidence verifying the structural basis of nanomolar affinity measured for two-prong inhibitors targeting the carbonic anhydrases.
| S-EPMC2527509 | biostudies-literature
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.
| S-EPMC5876008 | biostudies-literature