title: Inhibitory potential of prodomain of Plasmodium falciparum protease serine repeat antigen 5 for asexual blood stages of parasite.
abstract: Plasmodium falciparum serine repeat antigen 5 (SERA5) is a target for both drug and vaccine intervention against malaria. SERA5 is secreted in the parasitophorous vacuole where it is proteolytically processed before schizont rupture. Among the processed products is a 50.8-kDa central domain of the protease, which possesses chymotrypsin-like activity and consists of a 28.9-kDa catalytic domain with a 21.9-kDa N-terminal prodomain, which remain attached together. Because SERA5 has been implicated in merozoite egress from host erythrocytes, the effect of the prodomain and a heptapeptide derived from its C-terminus spanning from D(560) to F(566) (DNSDNMF) on parasite growth was studied. When E. coli-expressed prodomain was incubated with parasite culture, a significant delay in transition from schizont to ring stages was observed up to nanomolar concentrations. The peptide, DNSDNMF also showed similar effects but at nearly 1000-fold higher concentrations. The peptide was also found to interact with the catalytic domain. These data demonstrate the crucial role of SERA5 prodomain for the egress process. Given the inhibitory potential of the prodomain for the parasite, we suggest that peptidomimetic inhibitors based on SERA5 prodomain sequences can be developed as future therapeutics against malaria.
authors.affiliation: Malaria Research Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Asrar
authors.initials: A
authors.lastname: Alam
authors.forename: Virander S
authors.initials: VS
authors.lastname: Chauhan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D003001:Cloning, Molecular; D006801:Humans; D008018:Life Cycle Stages / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016778:Malaria, Falciparum / Q000097:blood* / Q000235:genetics / Q000469:parasitology; D008954:Models, Biological; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D011498:Protein Precursors / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D012100:Reproduction, Asexual / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D000953:Antigens, Protozoan; D000981:Antiprotozoal Agents; D011498:Protein Precursors; C480167:serine repeat antigen 5, Plasmodium falciparum; D010447:Peptide Hydrolases