Purine Salvage Pathways in the Apicomplexan Parasite Toxoplasma gondii

dc.contributor.authorChaudhary, Kshitiz
dc.contributor.authorDarling, John A.
dc.contributor.authorFohl, Leah M.
dc.contributor.authorSullivan, William J., Jr.
dc.contributor.authorDonald, Robert G. K.
dc.contributor.authorPfefferkorn, Elmer R.
dc.contributor.authorUllman, Buddy
dc.contributor.authorRoos, David S.
dc.contributor.departmentPharmacology and Toxicology, School of Medicine
dc.date.accessioned2024-08-29T16:12:32Z
dc.date.available2024-08-29T16:12:32Z
dc.date.issued2004
dc.description.abstractWe have exploited a variety of molecular genetic, biochemical, and genomic techniques to investigate the roles of purine salvage enzymes in the protozoan parasite Toxoplasma gondii. The ability to generate defined genetic knockouts and target transgenes to specific loci demonstrates that T. gondii uses two (and only two) pathways for purine salvage, defined by the enzymes hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK). Both HXGPRT and AK are single-copy genes, and either one can be deleted, indicating that either one of these pathways is sufficient to meet parasite purine requirements. Fitness defects suggest both pathways are important for the parasite, however, and that the salvage of adenosine is more important than salvage of hypoxanthine and other purine nucleobases. HXGPRT and AK cannot be deleted simultaneously unless one of these enzymes is provided in trans, indicating that alternative routes of functionally significant purine salvage are lacking. Despite previous reports to the contrary, we found no evidence of adenine phosphoribosyltransferase (APRT) activity when parasites were propagated in APRT-deficient host cells, and no APRT ortholog is evident in the T. gondii genome. Expression of Leishmania donovani APRT in transgenic T. gondii parasites yielded low levels of activity but did not permit genetic deletion of both HXGPRT and AK. A detailed comparative genomic study of the purine salvage pathway in various apicomplexan species highlights important differences among these parasites.
dc.eprint.versionFinal published version
dc.identifier.citationChaudhary K, Darling JA, Fohl LM, et al. Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii. J Biol Chem. 2004;279(30):31221-31227. doi:10.1074/jbc.M404232200
dc.identifier.urihttps://hdl.handle.net/1805/43044
dc.language.isoen_US
dc.publisherElsevier
dc.relation.isversionof10.1074/jbc.M404232200
dc.relation.journalJournal of Biological Chemistry
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectAdenine phosphoribosyltransferase
dc.subjectAdenosine kinase
dc.subjectHypoxanthine phosphoribosyltransferase
dc.subjectLeishmania donovani
dc.subjectRecombinant proteins
dc.subjectToxoplasma
dc.titlePurine Salvage Pathways in the Apicomplexan Parasite Toxoplasma gondii
dc.typeArticle
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