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

Andrea Angeli; Sonia Del Prete; Sameh M Osman; Fatmah A S Alasmary; Zeid AlOthman; William A Donald; Clemente Capasso; Claudiu T Supuran

doi:10.1080/14756366.2017.1422250

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

J Enzyme Inhib Med Chem. 2018 Dec;33(1):364-369. doi: 10.1080/14756366.2017.1422250.

Authors

Andrea Angeli¹, Sonia Del Prete^{1

2}, Sameh M Osman³, Fatmah A S Alasmary³, Zeid AlOthman³, William A Donald⁴, Clemente Capasso², Claudiu T Supuran^{1

3

4}

Affiliations

¹ a Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.
² b CNR , Istituto di Bioscienze e Biorisorse , Napoli , Italy.
³ c Department of Chemistry, College of Science , King Saud University , Riyadh , Saudi Arabia.
⁴ d School of Chemistry , University of New South Wales , Sydney , NSW , Australia.

Abstract

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 K_As ranging between 8.98 and 12.1 µM. L-His and D-Tyr showed medium potency activating effects, with K_As in the range of 17.6-18.2 µM, whereas other amines and amino acids were relatively ineffective activators, with K_As 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.

Keywords: Carbonic anhydrase; Mycobacterium tuberculosis; activators; metalloenzymes; pathogens.

MeSH terms

Amines / chemistry
Amines / metabolism*
Amino Acids / chemistry*
Amino Acids / metabolism*
Carbonic Anhydrases / genetics*
Carbonic Anhydrases / metabolism*
Molecular Structure
Mycobacterium tuberculosis / enzymology*
Mycobacterium tuberculosis / genetics

Substances

Amines
Amino Acids
Carbonic Anhydrases

Grants and funding

This research was financed in part by a Distinguished Scientist Fellowship Programme (DSFP) of King Saud University, Saudi Arabia to CTS. The Australian Research Council is also acknowledged for support [DP160102681].