Toxoplasma gondii is a protozoan parasite that can infect any warm-blooded animal, usually through contaminated food or cat feces. Although infection in healthy individuals is largely asymptomatic, the parasites can persist as latent cysts for extended periods, sometimes even for the entire life of the affected person. In pregnant women and immunocompromised individuals, including those with HIV/AIDS, T. gondii infection can cause severe disease, such as fatal encephalitis, an inflammation of the brain.
Researchers are studying T. gondii to identify potential targets for anti-infectives. Recently, a collaborative effort by a team of researchers from the NIAID-supported Seattle Structural Genomics Center for Infectious Diseases (SSGCID), the Fox Chase Cancer Center, and the University of Pennsylvania has resulted in the determination of the three-dimensional structure of one such target—the T. gondii porphobilinogen synthase (TgPBGS) protein.
PBGS is a metalloenzyme, or an enzyme containing a metal ion necessary for biological activity. PBGS has been structurally and biochemically characterized from many different species, including humans. A unique feature of the TgPBGS enzyme is the presence of an extended C-terminal tail region, which is essential for the formation of enzymatically active octameric protein, or protein with eight subunits. The crystal structure of TgPBGS reveals how the tail to tail interactions of TgPBGS cause octamer formation.
As this enzyme is essential for heme biosynthesis in Toxoplasma and is conserved in sequence and function in other apicomplexan parasites such as Plasmodium falciparum, the availability of this protein structure may facilitate the development of parasite species specific PBGS inhibitors.
J Biol Chem. 2011 Mar 7. Crystal structure of Toxoplasma gondii porphobilinogen synthase: insights on octameric structure and porphobilinogen formation. Jaffe EK, Shanmugan D, Gardberg A, Dieterich S, Sankaran B, Stewart LJ, Myler PJ, Roos DS.
For more information, please see the Protein Data Bank entry 3OBK.
All featured structures from the NIAID Structural Genomics Centers
Last Updated May 09, 2011