Sean Prigge is a professor with the Department of Molecular Microbiology and Immunology. His research focuses on enzymes and metabolic pathways in malaria parasites.
Malaria, a disease caused by protozoan parasites, is one of the most dangerous infectious diseases, claiming millions of lives and infecting hundreds of millions of people annually. Malaria parasites contain an essential organelle called the apicoplast that is thought to have arisen through endosymbiosis of an algal cell which had previously incorporated a cyanobacterium. Due to its prokaryotic origin, the apicoplast contains a range of metabolic pathways that differ significantly from those of the human host. We are investigating biochemical pathways found in the apicoplast, particularly those required for the biosynthesis and modification of fatty acids. This metabolism should require several enzyme cofactors such as pantothenate, lipoic acid, biotin and iron-sulfur clusters. We are interested in these cofactors, how they are acquired, how they are used, and whether they are essential for the growth of blood stage malaria parasites. We approach these questions with a combination of cell biology, genetic, biophysical and biochemical techniques.
Discovery of lipoate as an essential host factor
Jhun, M. S. Walters, and S. T. Prigge, Using lipoamidase as a novel probe to interrogate the importance of lipoylation in P. falciparum. mBio, 9, e01872-18 (2018). PMC6247088
G. A. Afanador, A. J. Guerra, R. P. Swift, R. E. Rodriguez, D. Bartee, K. A. Matthews, A. Schon, E. Freire, C. L. Freel Meyers, and S. T. Prigge, A novel lipoate attachment enzyme is shared by Plasmodium and Chlamydia species. Mol Micro, 106, 439-451 (2017). PMID28836704
G. A. Afanador, K. A. Matthews, D. Bartee, J. E. Gisselberg, M. S. Walters, C. L. Freel Meyers, and S. T. Prigge, Redox dependent lipoylation of mitochondrial proteins in Plasmodium falciparum. Mol Micro, 94, 156-171 (2014). PMC4177315
M. Allary, J. Z. Lu, L. Zhu, S. T. Prigge, Scavenging of the cofactor lipoate is essential for the survival of the malaria parasite Plasmodium falciparum. Mol. Micro. 63, 1331-1344 (2007). PMC2796473
Structural enzymology: How oxygen is activated by copper
E. E. Chufán, S. T. Prigge, X. Siebert, B. A. Eipper, R. E. Mains, L. M. Amzel. Differential reactivity between two copper sites in peptidylglycine α-hydroxylating monooxygenase. J. Am. Chem. Soc. 132, 15565-15572 (2010). PMC3025614
S. T. Prigge, R. E. Mains, B. A. Eipper, L. M. Amzel, Dioxygen binds end-on to mononuclear-copper in a precatalytic enzyme complex, Science 304, 864-867 (2004).
S. T. Prigge, A. S. Kolhekar, B. A. Eipper, R. E. Mains, L. M. Amzel, Substrate-mediated electron transfer in peptidylglycine alpha-hydroxylating monooxygenase, Nature Struct. Biol. 6, 976-983 (1999).
S. T. Prigge, A. S. Kolhekar, B. A. Eipper, R. E. Mains, L. M. Amzel, Amidation of Bioactive Peptides: The Structure of Peptidylglycine alpha-Hydroxylating Monooxygenase, Science 278, 1300-1305 (1997).
Essential role of protein posttranslational modifications in the apicoplast organelle
T. A. Dellibovi-Ragheb, H. Jhun, C. D. Goodman, M. S. Walters, D. R. T. Ragheb, K. A. Matthews, K. Rajaram, S. Mishra, G. I. McFadden, P. Sinnis and S. T. Prigge, Host biotin is required for liver stage development in malaria parasites. Proc Natl Acad Sci U S A, 115, E2604-E2613 (2018). PMC5856565
J. E. Gisselberg, T. A. Dellibovi-Ragheb, K. A. Matthews, G. Bosch and S. T. Prigge, The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. PLoS Pathog, 9, e1003655 (2013). PMC3784473
T. A. Dellibovi-Ragheb, J. E. Gisselberg and S. T. Prigge, Parasites FeS up: iron-sulfur cluster biogenesis in eukaryotic pathogens. PLoS Pathog, 9, e1003227 (2013). PMC3617024
Characterization and exploitation of Type II fatty acid biosynthesis in apicomplexan parasites
G. A. Afanador, S. P. Muench, M. McPhillie, A. Fomovska, A. Schon, Y. Zhou, G. Cheng, J. Stec, J. S. Freundlich, H. M. Shieh, J. W. Anderson, D. P. Jacobus, D. A. Fidock, A. P. Kozikowski, C. W. Fishwick, D. W. Rice, E. Freire, R. McLeod and S. T. Prigge, Discrimination of Potent Inhibitors of Toxoplasma gondii Enoyl-Acyl Carrier Protein Reductase by a Thermal Shift Assay. Biochemistry, 52, 9155-66 (2013). PMC3953223
J. R. Gallagher, K. A. Matthews, S. T. Prigge, Plasmodium falciparum apicoplast transit peptides are unstructured in vitro and during apicoplast import. Traffic, 12, 1124-1138 (2011). PMC3629917
J. R. Gallagher, S. T. Prigge, Plasmodium falciparum acyl carrier protein crystal structures in disulfide-linked and reduced states and their prevalence during blood stage growth. Proteins 78, 575-588 (2010). PMC2805782
S. T. Prigge, X. He, L. Gerena, N. C. Waters, K. A. Reynolds, The initiating steps of a Type II fatty acid synthase in Plasmodium falciparum are catalyzed by pfACP, pfMCAT and pfKASIII, Biochemistry 42, 1160-1169 (2003).