Thiol-containing protozoal proteins

Thiol-containing protozoal proteins represent a broad class of essential molecules in parasites such as Leishmania and Trypanosoma species that are characterized by the presence of reactive sulfhydryl (-SH) groups. These proteins include critical enzymes involved in redox homeostasis, such as trypanothione reductase, as well as glycolytic enzymes like glyceraldehyde-3-phosphate dehydrogenase and various zinc-finger transcription factors. The thiol groups are vital for the catalytic activity, structural integrity, and regulatory functions of these proteins, making them susceptible to inhibition by heavy metal-based drugs. Pentavalent antimonials and arsenical compounds exert their therapeutic effects by binding to these thiols, leading to the depletion of the parasite's antioxidant capacity and the inhibition of its energy metabolism. This multi-target mechanism is effective against protozoal infections but is also associated with significant host toxicity due to the presence of similar thiol groups in human proteins.

Other names

Sulfhydryl-containing protozoal proteinsProtozoal thiol groupsTrypanosomatid thiol-containing enzymes

Drugs such as pentavalent antimonials act as prodrugs that are reduced to trivalent antimony, which then binds to and inhibits various thiol-containing proteins and enzymes, disrupting the parasite's redox balance and energy metabolism.