The first activation study of the β-carbonic anhydrases from the pathogenic bacteria Brucella suis and Francisella tularensis with amines and amino acids

Journal of Enzyme Inhibition and Medicinal Chemistry

Mariana Pinteala¹  Bogdan C. Simionescu¹  Stelian S. Maier²  Sonia Del Prete³  Clemente Capasso³  Andrea Angeli⁴  Claudiu T. Supuran⁵  William A. Donald⁶ 

[1] Centre of Advanced Research in Bionanoconjugates and Biopolymers Department, “Petru Poni” Institute of Macromolecular Chemistry, Iasi, Romania;Centre of Advanced Research in Bionanoconjugates and Biopolymers Department, “Petru Poni” Institute of Macromolecular Chemistry, Iasi, Romania;Polymers Research Center, Polymeric Release Systems Research Group, “Gheorghe Asachi” Technical University of Iasi, Iasi, Romania;Istituto di Bioscienze e Biorisorse, CNR, Napoli, Italy;Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino, Italy;Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino, Italy;School of Chemistry, University of New South Wales, Sydney, Australi;School of Chemistry, University of New South Wales, Sydney, Australi;

关键词: Carbonic anhydrase;    metalloenzymes;    bacteria;    activators;    Brucella suis;   

DOI  :  10.1080/14756366.2019.1630617

来源: publisher

【 摘 要 】

The activation of the β-class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacteria Brucella suis and Francisella tularensis with amine and amino acids was investigated. BsuCA 1 was sensitive to activation with amino acids and amines, whereas FtuCA was not. The most effective BsuCA 1 activators were L-adrenaline and D-Tyr (KAs of 0.70–0.95 µM). L-His, L-/D-Phe, L-/D-DOPA, L-Trp, L-Tyr, 4-amino-L-Phe, dopamine, 2-pyridyl-methylamine, D-Glu and L-Gln showed activation constants in the range of 0.70–3.21 µM. FtuCA was sensitive to activation with L-Glu (KA of 9.13 µM). Most of the investigated compounds showed a weak activating effect against FtuCA (KAs of 30.5–78.3 µM). Many of the investigated amino acid and amines are present in high concentrations in many tissues in vertebrates, and their role in the pathogenicity of the two bacteria is poorly understood. Our study may bring insights in processes connected with invasion and pathogenic effects of intracellular bacteria.

【 授权许可】

CC BY