Synthetic peptides derived from the C-terminal 6kDa region of Plasmodium falciparum SERA5 inhibit the enzyme activity and malaria parasite development

Kanodia, Shivani; Kumar, Gagan; Rizzi, Luca; Pedretti, Alessandro; Hodder, Anthony N.; Romeo, Sergio; Malhotra, Pawan

doi:10.1016/j.bbagen.2014.04.013

Cited by 22 publications

(32 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although PfMSP3 is abundantly expressed on the merozoite surface, it is still uncertain how this protein is associated with the merozoite surface. To establish the PfMSP3-associated network on the Plasmodium merozoite surface, we carried out a detailed protein-protein interaction analysis by performing immuno-pulldown of parasite lysate proteins using antibodies against an rMSP3 N-terminal fragment, a technique previously used to identify proteinprotein interactions (28,34,39,40). Five parasite proteins, MSP1, MSP6, MSP7, RAP2, and SERA5, which may be directly or indirectly involved in the invasion process were identified together with MSP3 in four independent LC-MS/MS experiments.…”

Section: Discussionmentioning

confidence: 99%

“…The expressed proteins were confirmed by Western blotting with monoclonal anti-His antibody (Sigma). The rMSP1 65 (consisting of aa 1052 to 1664 of MSP1) and rSERA5 proteins along with their specific anti-rabbit sera were based on Paul et al and Kanodia et al,respectively (28,34).…”

Section: Methodsmentioning

confidence: 99%

“…S2 in the supplemental material) and subsequently used to generate specific antisera in mice and rabbits. Fragments of MSP1 protein consisting of aa 1052 to 1664, designated MSP1 65 , and SERA5 (serine repeat antigen 5) were generated as described previously (28,34). The five antisera were used to study the colocalization of these proteins on merozoites using immunofluorescence assay (IFA).…”

Section: Msp3 Localizes On Merozoite Surface In Association With Msp1mentioning

confidence: 99%

See 2 more Smart Citations

Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

et al. 2018

Self Cite

View full text Add to dashboard Cite

merozoite surface protein 3 (MSP3) is an abundantly expressed secreted merozoite surface protein and a leading malaria vaccine candidate antigen. However, it is unclear how MSP3 is retained on the surface of merozoites without a glycosylphosphatidylinositol (GPI) anchor or a transmembrane domain. In the present study, we identified an MSP3-associated network on the merozoite surface by immunoprecipitation of merozoite lysate using antibody to the N terminus of MSP3 (anti-MSP3N) followed by mass spectrometry analysis. The results suggested the association of MSP3 with other merozoite surface proteins: MSP1, MSP6, MSP7, RAP2, and SERA5. Protein-protein interaction studies by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analysis showed that MSP3 complex consists of MSP1, MSP6, and MSP7 proteins. Immunological characterization of MSP3 revealed that MSP3N is strongly recognized by hyperimmune serum from African and Asian populations. Furthermore, we demonstrate that human antibodies, affinity purified against recombinant MSP3N (rMSP3N), promote opsonic phagocytosis of merozoites in cooperation with monocytes. At nonphysiological concentrations, anti-MSP3N antibodies inhibited the growth of Together, the data suggest that MSP3 and especially its N-terminal region containing known B/T cell epitopes are targets of naturally acquired immunity against malaria and also comprise an important candidate for a multisubunit malaria vaccine.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Msp3 Localizes On Merozoite Surface In Association With Msp1mentioning

confidence: 99%

See 1 more Smart Citation

Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Next we evaluated the possible role of phosphorylation in the modulation of protease activity of PfSERA5. Recombinant PfSERA5 50 has been shown to cleave LLVY-AMC, a synthetic fluorescent peptide substrate (13,22). Using LLVY-AMC as a substrate, we analyzed the activity of recombinant PfSERA5 50 after incubation with recombinant PfCDPK1 in the presence or absence of Ca 2ϩ .…”

Section: Pfcdpk1 Phosphorylates Pfsera5 and Enhances Its Protease Actmentioning

confidence: 99%

“…Inhibitors of PfSUB1, an enzyme involved in PfSERA5 processing, stalls merozoite egress and parasite maturation, suggesting that PfSERA5 and its processing enzyme PfSUB1 are important drug targets (11,12). Although PfSERA5 is highly expressed at the late schizont stage, its proteolytic activity has been an issue of debate because of low proteolytic activity displayed by recombinant PfSERA5 expressed in Escherichia coli (13,22). A few recent studies have suggested that PfSERA5 serves as a pseudoprotease that regulates the kinetics/efficiency of P. falciparum merozoite egress from mature schizonts (23,24).…”

mentioning

confidence: 99%

Calcium-dependent phosphorylation of Plasmodium falciparum serine repeat antigen 5 triggers merozoite egress

Iyer

Singh

Kaur

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The human malaria parasite proliferates in red blood cells following repeated cycles of invasion, multiplication, and egress. serine repeat antigen 5 (PfSERA5), a putative serine protease, plays an important role in merozoite egress. However, regulation of its activity leading to merozoite egress is poorly understood. In this study, we show that PfSERA5 undergoes phosphorylation prior to merozoite egress. Immunoprecipitation of parasite lysates using anti-PfSERA5 serum followed by MS analysis identified calcium-dependent protein kinase 1 (PfCDPK1) as an interacting kinase. Association of PfSERA5 with PfCDPK1 was corroborated by co-sedimentation, co-immunoprecipitation, and co-immunolocalization analyses. Interestingly, PfCDPK1 phosphorylated PfSERA5 in the presence of Ca and enhanced its proteolytic activity. A PfCDPK1 inhibitor, purfalcamine, blocked the phosphorylation and activation of PfSERA5 both as well as in schizonts, which, in turn, blocked merozoite egress. Together, these results suggest that phosphorylation of PfSERA5 by PfCDPK1 following a rise in cytosolic Ca levels activates its proteolytic activity to trigger merozoite egress.

show abstract

The Nϵ‐Rule for Serine, but Not Cysteine Catalytic Triads

Czapinska

Bochtler

2022

Angewandte Chemie

View full text Add to dashboard Cite

Catalytic triads, composed of a serine or cysteine nucleophile, a histidine, and a third triad residue (typically Asp/Glu/Asn), are common in enzyme active sites and catalyze a wide variety of chemical reactions. Two types of triads can be distinguished: We refer to them as Nδ-or Nɛ-configured, depending on whether the histidine imidazole Nδ or Nɛ atom is close to the nucleophile Oγ/Sγ. In this study, we have analyzed triad configuration. In structural triads, the more stable Nδ-configuration predominates. For catalytic triads, the configuration depends on the nucleophile. When it is a cysteine residue, both configuration types occur, depending on the family. However, when the nucleophile is a serine residue, the less stable Nɛ-configuration is almost exclusively found. We posit that the energetically less favored conformation is selected for in serine triads to facilitate the otherwise difficult proton transfer from the nucleophile to the histidine residue.

show abstract

Synthetic peptides derived from the C-terminal 6kDa region of Plasmodium falciparum SERA5 inhibit the enzyme activity and malaria parasite development

Cited by 22 publications

References 42 publications

Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

Calcium-dependent phosphorylation of Plasmodium falciparum serine repeat antigen 5 triggers merozoite egress

The Nϵ‐Rule for Serine, but Not Cysteine Catalytic Triads

Contact Info

Product

Resources

About