Anion Inhibition Profile of the β-Carbonic Anhydrase from the Opportunist Pathogenic Fungus Malassezia restricta Involved in Dandruff and Seborrheic Dermatitis

Metabolites

Clemente Capasso¹  SoniaDel Prete¹  Cynthia Ghobril²  Julien Hitce²  Xavier Marat²  Cécile Clavaud²  Andrea Angeli³  ClaudiuT. Supuran³ 

[1] Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, I-80131 Napoli, Italy;L’Oréal Research and Innovation, 93601 Aulnay-sous-Bois, France;Sezione di Scienze Farmaceutiche e Nutraceutiche, Dipartimento Neurofarba, Università degli Studi di Firenze, Via U. Schiff 6, I-50019 Sesto Fiorentino, Florence, Italy;

关键词: carbonic anhydrases;    metalloenzymes;    anions;    CA inhibitors;    Malassezia restricta;    Malassezia globosa;    dandruff;    seborrheic dermatitis;   

DOI  :  10.3390/metabo9070147

来源: DOAJ

【 摘 要 】

Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes, which catalyze the crucial physiological CO₂ hydration/dehydration reaction (CO₂ + H₂O ⇌ HCO₃⁻ + H⁺) balancing the equilibrium between CO₂, H₂CO₃, HCO₃⁻ and CO₃²⁻. It has been demonstrated that their selective inhibition alters the equilibrium of the metabolites above affecting the biosynthesis and energy metabolism of the organism. In this context, our interest has been focalized on the fungus Malassezia restricta, which may trigger dandruff and seborrheic dermatitis altering the complex bacterial and fungal equilibrium of the human scalp. We investigated a rather large number of inorganic metal-complexing anions (a well-known class of CA inhibitors) for their interaction with the β-CA (MreCA) encoded by the M. restricta genome. The results were compared with those obtained for the two human α-CA isoforms (hCAI and hCAII) and the β-CA from Malassezia globosa. The most effective MreCA inhibitors were diethyldithiocarbamate, sulfamide, phenyl arsenic acid, stannate, tellurate, tetraborate, selenocyanate, trithiocarbonate, and bicarbonate. The different K_I values obtained for the four proteins investigated might be attributed to the architectural features of their catalytic site. The anion inhibition profile is essential for better understanding the inhibition/catalytic mechanisms of these enzymes and for designing novel types of inhibitors, which may have clinical applications for the management of dandruff and seborrheic dermatitis.

【 授权许可】

Unknown