Trypanosoma cruzi proline racemase (TcPRAC) (TcPRAC)

Trypanosoma cruzi proline racemase (TcPRAC) is an essential enzyme in the life cycle of the parasite responsible for Chagas disease (Chamond et al., 2003, PubMed: 12624190). It exists in two distinct isoforms: TcPRAC1, which is secreted by the parasite, and TcPRAC2, which remains intracellular (Reina-San-Martin et al., 2000, PubMed: 10859348). The secreted isoform functions as a potent B-cell mitogen, inducing a non-specific polyclonal activation that helps the parasite evade the host's specific immune response. The intracellular isoform is involved in critical metabolic pathways and parasite differentiation (Coatnoan et al., 2001, PubMed: 11470795). The enzyme catalyzes the interconversion of L-proline and D-proline, a reaction that is absent in human biology as humans lack the proline racemase gene (Buschiazzo et al., 2006, PubMed: 16824301). This absence makes TcPRAC a highly attractive and selective target for the development of new trypanocidal drugs. Small molecule inhibitors, such as pyrrole-2-carboxylic acid, have been shown to bind the active site and inhibit the enzyme's activity, effectively neutralizing its mitogenic and metabolic functions (Minotto et al., 2001, PubMed: 11555651).

Other names

Proline racemaseTcPRAC1TcPRAC2B-cell mitogen

Competitive inhibition of the enzyme active site, preventing the interconversion of L-proline and D-proline and blocking B-cell mitogenic activity.