Dithiocarbamates with potent inhibitory activity against the<i>Saccharomyces cerevisiae</i><b>β</b>-carbonic anhydrase

Bozdağ, Murat; Carta, Fabrizio; Vullo, Daniela; Işık, Semra; ALOthman, Zeid A.; Osman, Sameh M.; Scozzafava, Andrea; Supuran, Claudiu T.

doi:10.3109/14756366.2015.1010529

Cited by 18 publications

(11 citation statements)

References 56 publications

(82 reference statements)

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“…One of the most abundant zinc enzymes in the blood is carbonic anhydrase (CA, EC 4.2.1.1), which catalyzes a simple but essential reaction in all life kingdoms, CO 2 hydration to bicarbonate and protons 1–4 . This reaction, or the three chemical entities involved in it, carbon dioxide, bicarbonate and protons, are important for the pH regulation and homeostasis of the organism, CO 2 and HCO 3 − transport in several biosynthetic processes, for the production of body fluids, bone resorption, tumorigenicity, and other physiological processes in vertebrates, whereas in some bacteria, plants and algae they are involved in photosynthetic processes 5–7 .…”

Section: Introductionmentioning

confidence: 99%

Dioxygen, an unexpected carbonic anhydrase ligand

Ferraroni

Gaspari

Scozzafava

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes, grouped into seven different classes, which catalyze the reaction of CO2 hydration to bicarbonate and protons. All of the fifteen human isoforms reported to date belong to the α-class and contain zinc as a cofactor. The structure of human Zn,Cu-CA II has been solved which contains a copper ion bound at its N-terminal, coordinated to His4 and His64. In the active site a dioxygen molecule is coordinated to the zinc ion. Since dioxygen is a rather unexpected CA ligand, molecular dynamics (MD) simulations were performed which suggested a superoxide character of the zinc bound O2.

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Section: Introductionmentioning

confidence: 99%

Dioxygen, an unexpected carbonic anhydrase ligand

Ferraroni

Gaspari

Scozzafava

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…These findings suggest a link between cAMP signaling and CO 2 /HCO À 3 sensing capable of influencing the fungal metabolism and pathogenesis [33][34][35][36] . Nonpathogenic and pathogenic fungi, such as Saccharomyces cerevisiae, C. albicans and C. glabrata, present only a single copy of CA belonging to a b-CA class; while in other fungi it is possible to find multiple copies of b-CA-and a-CA-encoding genes 29,[37][38][39] . Candida albicans CA, CaNce103, and the analogous CA, CgNce103, encoded by the genome of C. glabrata, are essential for pathogenesis of these fungi in niches where the available CO 2 is limited (e.g.…”

Section: Introductionmentioning

confidence: 99%

A new procedure for the cloning, expression and purification of the β-carbonic anhydrase from the pathogenic yeastMalassezia globosa, an anti-dandruff drug target

Prete

Luca

Vullo

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Malassezia yeasts are almost exclusively the single eukaryotic members of the fungal flora of the skin. Malassezia globosa and Malassezia restricta are found on the skin of practically all humans. Malassezia globosa is highly implicated in the pathogenesis of dandruff and its genome encodes for only one carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the b-class (MgCA). It has been indeed demonstrated that in many pathogenic microorganisms, CAs are essential for their life cycle and their inhibition can lead to growth impairment and defects. In the previous work, the recombinant MgCA was investigated for its inhibition profile with sulfonamides, which in models of dandruff infection were able to protect animals from the fungal infection, allowing us to propose this enzyme as a new antidandruff target. MgCA was cloned as GST-fusion protein, but the yield was rather low and the protein was often found in inclusion bodies. Here, we propose an alternative procedure consisting in cloning the recombinant MgCA as His-Tag fusion protein. This procedure resulted in a good method to express and purify the active recombinant MgCA, and the protein recovery was better with respect to that used for preparing MG-CA (b-CA cloned as GST-fusion protein).

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“…CAIs possessing different inhibition mechanisms compared to the classical inhibitors were reported in the last years 34,35 . The interest in CAIs is mainly motivated by their pharmacological properties and clinical use as diuretics, antiglaucoma, antiobesity or antiepileptic agents, as well as anticancer agents and diagnostic tools [36][37][38] . The neurotransmitter acetylcholine (ACh) mediates its physiological effects via a plethora of receptors expressed throughout the central nervous system and the peripheral nervous system 39,40 .…”

Section: Introductionmentioning

confidence: 99%