Beta-carbonic anhydrase 3 (mtbCA3)

Mycobacterium tuberculosis beta-carbonic anhydrase 3 (mtbCA3), encoded by the gene Rv0105, is one of three beta-class carbonic anhydrases identified in the Mycobacterium tuberculosis genome (UniProt: P9WIB1). This enzyme catalyzes the reversible hydration of carbon dioxide to bicarbonate and protons, a process fundamental for maintaining the bacterium's internal pH and supplying bicarbonate for vital metabolic processes, including the synthesis of fatty acids and amino acids (PubMed: 23621516). Because mtbCA3 belongs to the beta-class, it is structurally distinct from the alpha-class carbonic anhydrases found in humans, offering a significant opportunity for the design of highly selective antitubercular drugs that do not interfere with host physiology. Research into mtbCA3 inhibitors, such as sulfonamides, sulfamates, and coumarins, has shown that these compounds can effectively bind the enzyme's zinc-containing active site and inhibit its activity (PubMed: 24754593). Although some studies suggest mtbCA3 may not be essential for growth under all laboratory conditions, its role in survival during different stages of the infection cycle and its synergy with other CA isoforms make it a subject of significant interest in the search for novel treatments for drug-resistant tuberculosis (PubMed: 25164478). Development efforts focus on improving the lipophilicity of inhibitors to ensure they can penetrate the dense, waxy cell wall of the tubercle bacillus while maintaining high specificity for the bacterial enzyme over human homologs.

Other names

Rv0105Carbonate dehydratase 3Carbonic anhydrase 3β-CA3Mycobacterium tuberculosis beta-carbonic anhydrase 3

Inhibition of the enzymatic hydration of carbon dioxide, leading to the disruption of intracellular pH homeostasis and the depletion of bicarbonate required for essential mycobacterial biosynthetic pathways (PubMed: 25164478).