Cyclopropane mycolic acid synthase 2 (CmaA2)

Cyclopropane mycolic acid synthase 2 (CmaA2) is an S-adenosylmethionine-dependent methyltransferase in Mycobacterium tuberculosis, encoded by the gene Rv0503 (UniProt P0A5P1, P9WPB3). It plays a specialized role in the biosynthesis of mycolic acids, which are long-chain fatty acids that form the primary structural and functional component of the mycobacterial cell envelope (Glickman MS, 2001). Specifically, CmaA2 catalyzes the trans-cyclopropanation of the proximal position of oxygenated mycolic acids, such as methoxymycolates and ketomycolates (Barkan D, et al., 2010). These modifications are essential for maintaining the permeability of the cell wall and are critical for the bacterium's ability to persist within the host and modulate the host's immune response (Glickman MS, 2001). While CmaA2 is not the primary target of current first-line tuberculosis therapies, it is a validated target for the development of new anti-tubercular drugs aimed at disrupting cell wall assembly (Barkan D, et al., 2010). Research has demonstrated that tool compounds like dioctylamine can inhibit its activity in vitro, and the loss of CmaA2 function can lead to significant changes in the inflammatory properties of the cell wall, which in some models has been associated with a hypervirulent phenotype (Rao V, et al., 2006).

Other names

CMAS2Rv0503trans-cyclopropane synthetaseCyclopropane-fatty-acyl-phospholipid synthase 2Mycolic acid methyltransferase

Inhibition of the S-adenosylmethionine-dependent methyltransferase activity, preventing the formation of trans-cyclopropane rings in mycolic acids.