Activation studies with amines and amino acids of the β-carbonic anhydrase encoded by the Rv3273 gene from the pathogenic bacterium Mycobacterium tuberculosis

Journal of Enzyme Inhibition and Medicinal Chemistry

Clemente Capasso¹  Sameh M. Osman²  Zeid AlOthman²  Fatmah A. S. Alasmary²  Andrea Angeli³  Sonia Del Prete⁴  Claudiu T. Supuran⁵  William A. Donald⁶ 

[1] CNR, Istituto di Bioscienze e Biorisorse, Napoli, Italy;Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia;Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Florence, Italy;Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Florence, Italy;CNR, Istituto di Bioscienze e Biorisorse, Napoli, Italy;Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Florence, Italy;Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia;School of Chemistry, University of New South Wales, Sydney, NSW, Australi;School of Chemistry, University of New South Wales, Sydney, NSW, Australi;

关键词: Carbonic anhydrase;    metalloenzymes;    pathogens;    activators;    Mycobacterium tuberculosis;   

DOI  :  10.1080/14756366.2017.1422250

来源: publisher

【 摘 要 】

The activation of a β-class carbonic anhydrase (CAs, EC 4.2.1.1) from Mycobacterium tuberculosis, encoded by the gene Rv3273 (mtCA 3), was investigated using a panel of natural and non-natural amino acids and amines. mtCA 3 was effectively activated by D-DOPA, L-Trp, dopamine and serotonin, with KAs ranging between 8.98 and 12.1 µM. L-His and D-Tyr showed medium potency activating effects, with KAs in the range of 17.6–18.2 µM, whereas other amines and amino acids were relatively ineffective activators, with KAs in the range of 28.9–52.2 µM. As the physiological roles of the three mtCAs present in this pathogen are currently poorly understood and considering that inhibition of these enzymes has strong antibacterial effects, discovering molecules that modulate their enzymatic activity may lead to a better understanding of the factors related to the invasion and colonisation of the host during Mycobacterium tuberculosis infection.

【 授权许可】

CC BY