Disease relevance of MAL3P5.5

• Immunogenicity of the Plasmodium falciparum serine repeat antigen (p126) expressed by vaccinia virus [1].
• The crystal structure reveals a tetramer with a sulphate ion bound in the cofactor-binding site such that the side chains of the catalytic triad of serine, tyrosine and lysine are aligned in an active conformation, as previously observed in the Escherichia coli OAR-NADP+ complex [2].

High impact information on MAL3P5.5

• The P.falciparum transit peptide is exceptional compared with other known plastid transit peptides in not requiring serine or threonine residues [3].
• In addition to its synthesis from choline, phosphatidylcholine is synthesized from serine via an unknown pathway [4].
• Serine, which is actively transported by Plasmodium from human serum and readily available in the parasite, is subsequently converted into phosphoethanolamine [4].
• The process of human erythrocyte invasion by Plasmodium falciparum parasites involves a calcium-dependent serine protease with properties consistent with a subtilisin-like activity [5].
• Instead of the known serine-to-asparagine change at position 108 that is important in pyrimethamine resistance, a serine-to-threonine change at the same position is found in cycloguanil-resistant isolates along with an alanine-to-valine change at position 16 [6].

Chemical compound and disease context of MAL3P5.5

• Based on investigations on several blood stage antigens from Plasmodium falciparum we have expressed a hybrid protein in E. coli containing 262 amino acids of the serine-stretch protein SERP and 189 amino acids of the histidine alanine rich protein HRPII [7].

Biological context of MAL3P5.5

• Mutation of the predicted active site serine abolished processing [8].
• Isolation and deduced amino acid sequence of the gene encoding gp115, a yeast glycophospholipid-anchored protein containing a serine-rich region [9].
• Our results indicate the presence on the merozoite surface of a multifunctional serine sheddase with a broad substrate specificity [10].
• These antibodies were used to clone the gene encoding a serine protease using a B. divergens cDNA library [11].
• Unlike humans and yeast, Plasmodium falciparum, the agent of the most severe form of human malaria, utilizes host serine as a precursor for the synthesis of phosphatidylcholine via a plant-like pathway involving phosphoethanolamine methylation [12].

Anatomical context of MAL3P5.5

• A subset of serine protease inhibitors blocks the processing and shedding of both AMA-1 and TRAP and inhibits sporozoite infectivity, suggesting that interfering with sporozoite proteolytic processing may constitute a valuable strategy to prevent hepatocyte infection [13].
• As SERA-5 and some other serine-repeat antigens localise to the parasitophorous vacuole in mature parasites, they may play a role in erythrocyte rupture [14].
• In the present work, we intend to determine the capacity of human lymphocytes to recognize subfragments of the serine-stretch protein SERP, a blood-stage antigen from Plasmodium falciparum [15].
• We have previously identified a Plasmodium falciparum protein belonging to the superfamily of subtilisin-like serine proteases, which is expressed in a subset of secretory organelles in free merozoites [16].
• Inhibition studies using synthetic peptides derived from the presumed band 3 enzymatic cleavage sites and the observed uptake of fluorescent phospholipids following gp76 treatment, suggest that band 3 degradation by this serine protease participates in the formation of the parasitophorous vacuole by restructuring the red cell cytoskeleton [17].

Associations of MAL3P5.5 with chemical compounds

• The unusual concentration of 27 serines in the COOH-terminal portion of the protein shares homology with a similar polyserine repeat of the serine repeat antigen (SERA protein) of Plasmodium falciparum [9].
• The synthesis of this phospholipid occurs via two routes, the CDP-choline pathway, which uses host choline as a precursor, and the plant-like serine decarboxylase-phosphoethanolamine methyltransferase (SDPM) pathway, which uses host serine as a precursor [18].
• An apparent plateau was then reached for all metabolites except intracellular serine and Etn [19].
• No concomitant inhibition of PtdSer or PtdCho labelling from serine occurred, even when PtdEtn formation was decreased by 95% [19].
• In addition, the 120-kDa serine repeat antigen known as SERA, which was determined to be present on the merozoite, bound to phosphatidylserine vesicles and much less to vesicles of other phospholipids [20].

Physical interactions of MAL3P5.5

• Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1 [21].

Other interactions of MAL3P5.5

• Remarkably, this cleavage is mediated by the same membrane-bound parasite serine protease as that responsible for shedding of the merozoite surface protein-1 (MSP-1) complex, an abundant, glycosylphosphatidylinositol-anchored multiprotein complex [10].

Analytical, diagnostic and therapeutic context of MAL3P5.5

• Immune responses induced by gene gun or intramuscular injection of DNA vaccines that express immunogenic regions of the serine repeat antigen from Plasmodium falciparum [22].
• Molecular cloning, genomic structure and localization in a blood stage antigen of Plasmodium falciparum characterized by a serine stretch [23].
• We showed that 47% of 141 DHFR gene PCR products had Serine (wild phenotype), and 52% had Asparagine [24].
• Sequencing of the in vivo treatment failure revealed a point mutation at codon 268 resulting in an amino acid change from tyrosine to serine [25].

References