title: Structural rationale for the recognition of arginine at P₃ in PEXEL motif containing proteins of Plasmodium falciparum by plasmepsin V.
abstract: The virulent form of malaria is caused by Plasmodium falciparum that infects red blood cells. In order to survive inside the host, the parasite remodels the infected erythrocytes by exporting more than 300 effector proteins outside the parasitophorous vacuole membrane into the cytosol. The main feature of all the export proteins is the presence of a pentapeptide sequence motif; RxLxE/Q/D. This sequence motif is hydrolysed between L-x and the proteins with the acetylated new N-terminus xE/Q/D are exported. The enzyme responsible for this hydrolysis is plasmepsin V which is one of the ten aspartic proteases in P. falciparum. In order to understand the structural rationale for the specificity of this protease towards cleavage of the above motif, we generated three-dimensional models of seven plasmepsins (I, V to X) for which experimental structures are not available and compared these along with the crystal structures of three P. falciparum plasmepsins (II to IV). The structure comparisons revealed the importance of Tyr13, Glu77 and Ala117 specific to plasmepsin V that facilitates the accommodation of arginine at P₃ in the RxLxE/Q/D motif. Our analysis correlates the structure-function relationship of plasmepsin V.
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500046, India. lgpsc@uohyd.ernet.in
authors.forename: Lalitha
authors.initials: L
authors.lastname: Guruprasad
authors.forename: Karunakar
authors.initials: K
authors.lastname: Tanneeru
authors.forename: Kunchur
authors.initials: K
authors.lastname: Guruprasad
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010436:Pepstatins / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D010436:Pepstatins; D015800:Protozoan Proteins; D001120:Arginine; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin; C031375:pepstatin