Journal article

Inhibition of malaria parasite development by a cyclic peptide that targets the vital parasite protein SERA5

W Douglas Fairlie, Tim P Spurck, Joanne E McCoubrie, Paul R Gilson, Susanne K Miller, Geoffrey I McFadden, Robyn Malby, Brendan S Crabb, Anthony N Hodder

INFECTION AND IMMUNITY | AMER SOC MICROBIOLOGY | Published : 2008

Abstract

The serine repeat antigen (SERA) proteins of the malaria parasites Plasmodium spp. contain a putative enzyme domain similar to that of papain family cysteine proteases. In Plasmodium falciparum parasites, more than half of the SERA family proteins, including the most abundantly expressed form, SERA5, have a cysteine-to-serine substitution within the putative catalytic triad of the active site. Although SERA5 is required for blood-stage parasite survival, the occurrence of a noncanonical catalytic triad casts doubt on the importance of the enzyme domain in this function. We used phage display to identify a small (14-residue) disulfide-bonded cyclic peptide (SBP1) that targets the enzyme domai..

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Grants

Funding Acknowledgements

This work was funded by an NHMRC of Australia program grant (to B.S.C. and G.I.M.), fellowship (to W.D.F.), and Dora Lush Scholarship (to J.E.M.). B.S.C. and G.I.M. are International Researchers of the Howard Hughes Medical Institute.We acknowledge Dean Goodman for his assistance in the preparation of parasites for growth assays. We also thank Manuel Baca for provision of phage expression vectors and Peter Colman for critical evaluation of the manuscript. We thank the Australian Red Cross for the supply of blood.