Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec;35(1):824-830.
doi: 10.1080/14756366.2020.1743284.

Activation studies of the β-carbonic anhydrases from Malassezia restricta with amines and amino acids

Andrea Angeli  1 , Sonia Del Prete  2 , Cynthia Ghobril  3 , Julien Hitce  3 , Cécile Clavaud  3 , Xavier Marrat  3 , William A Donald  4 , Clemente Capasso  2 , Claudiu T Supuran  1   4
Affiliations

Activation studies of the β-carbonic anhydrases from Malassezia restricta with amines and amino acids

Andrea Angeli et al. J Enzyme Inhib Med Chem. 2020 Dec.

Abstract

The β-carbonic anhydrase (CA, EC 4.2.1.1) from the genome of the opportunistic pathogen Malassezia restricta (MreCA), which was recently cloned and characterised, herein has been investigated for enzymatic activation by a panel of amines and amino acids. Of the 24 compounds tested in this study, the most effective MreCA activators were L-adrenaline (KA of 15 nM), 2-aminoethyl-piperazine/morpholine (KAs of 0.25-0.33 µM), histamine, L-4-amino-phenylalanine, D-Phe, L-/D-DOPA, and L-/D-Trp (KAs of 0.32 - 0.90 µM). The least effective activators were L-/D-Tyr, L-Asp, L-/D-Glu, and L-His, with activation constants ranging between 4.04 and 12.8 µM. As MreCA is involved in dandruff and seborrhoeic dermatitis, these results are of interest to identify modulators of the activity of enzymes involved in the metabolic processes of such fungi.

Keywords: Carbonic anhydrase; activator; amine; amino acid; pathogenic fungi; β-class enzyme.

PubMed Disclaimer

Conflict of interest statement

The authors have no relevant affiliations of financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Figures

Figure 1.
Figure 1.
Amino acids and amines 1–24 investigated as CAAs in the present article.
See this image and copyright information in PMC

References

    1. (a) Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 2008;7:168–81. - PubMed
    2. (b) Nocentini A, Supuran CT.. Advances in the structural annotation of human carbonic anhydrases and impact on future drug discovery. Expert Opin Drug Discov 2019;14:1175–97. - PubMed
    1. (a) Supuran CT. How many carbonic anhydrase inhibition mechanisms exist?. J Enzyme Inhib Med Chem 2016;31:345–60. - PubMed
    2. (b) Supuran CT. Advances in structure-based drug discovery of carbonic anhydrase inhibitors. Expert Opin Drug Discov 2017;12:61–88. (c) Supuran CT. Structure and function of carbonic anhydrases. Biochem J 2016;473: 2023–32. - PubMed
    1. (a) Supuran CT. Carbonic anhydrase activators. Future Med Chem 2018;10:561–73. - PubMed
    2. (b) Temperini C, Scozzafava A, Supuran CT.. Carbonic anhydrase activation and the drug design. Curr Pharm Des 2008;14:708–15. (c) Akocak S, Supuran CT.. Activation of α-, β-, γ- δ-, ζ- and η- class of carbonic anhydrases with amines and amino acids: a review. J Enzyme Inhib Med Chem 2019;34: 1652–9. - PubMed
    1. (a) Zoccola D, Innocenti A, Bertucci A, et al. . Coral carbonic anhydrases: regulation by ocean acidification. Mar Drugs 2016;14:109. - PMC - PubMed
    2. (b) Bertucci A, Moya A, Tambutté S, et al. . Carbonic anhydrases in anthozoan corals – a review. Bioorg Med Chem 2013;21:1437–50. (c) Del Prete S, Vullo D, Zoccola D, et al. . Activation profile analysis of CruCA4, an α-carbonic anhydrase involved in skeleton formation of the mediterranean red coral, Corallium rubrum. Molecules 2017;23: 66,.(d) Dathan NA, Alterio V, Troiano E, et al. . Biochemical characterization of the chloroplastic β-carbonic anhydrase from Flaveria bidentis (L.) "Kuntze". J Enzyme Inhib Med Chem 2014;29: 500–4.
    1. (a) Capasso C, Supuran CT.. An overview of the alpha-, beta- and gamma-carbonic anhydrases from Bacteria: can bacterial carbonic anhydrases shed new light on evolution of bacteria?. J Enzyme Inhib Med Chem 2015;30:325–32. - PubMed
    2. (b) Smith KS, Jakubzick C, Whittam TS, Ferry JG.. Carbonic anhydrase is an ancient enzyme widespread in prokaryotes. Proc Natl Acad Sci USA 1999;96:15184–9. - PMC - PubMed

MeSH terms