Proximal cyclopropane synthase of mycolic acids (PcaA) (PcaA)

Proximal cyclopropane synthase of mycolic acids (PcaA) is an essential S-adenosyl-L-methionine (SAM)-dependent methyltransferase in Mycobacterium tuberculosis. It is responsible for the site-specific cyclopropanation of the proximal position of alpha-mycolic acids, which are critical components of the mycobacterial cell wall. This modification is vital for the structural integrity of the cell envelope and plays a significant role in the pathogen's virulence and its ability to persist during chronic infection. Research indicates that PcaA is required for the characteristic cording morphology of M. tuberculosis and for inducing a proinflammatory response in the host. Because PcaA has no human homolog and is crucial for bacterial survival and pathogenesis, it is a highly attractive target for the development of novel antitubercular drugs. Inhibiting PcaA destabilizes the cell wall, making the bacteria more susceptible to host immune defenses and potentially enhancing the activity of other antibiotics. (Sources: UniProt P9WIP5; Glickman et al., 2000, J. Exp. Med.; Huang et al., 2002, J. Biol. Chem.; Barkan et al., 2012, Chem. Biol.)

Other names

Cyclopropane mycolic acid synthase 4CMAS4Rv0470Protein PcaAMycolic acid methyltransferase

Inhibition of the S-adenosyl-L-methionine-dependent cyclopropanation of the proximal position of alpha-mycolic acids, which disrupts the integrity of the mycobacterial cell wall and reduces the pathogen's ability to persist during chronic infection.