4zl4

Plasmepsin V from Plasmodium vivax bound to a transition state mimetic (WEHI-842)

spinqualitylabelsall models 4zl4, resolution 2.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zl4 is a 2 chain structure with sequence from Plasmodium vivax. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.37Å Ligands: 4PF, 4PK, EDO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PLM5_PLAVS During the asexual blood stage, plays an essential role in the export of several proteins into the host erythrocytes by cleaving the pentameric localization motif RxLxE/Q/D (termed Plasmodium export element (PEXEL)) located downstream of the N-terminal secretory signal sequence (PubMed:24983235). Specifically, cleaves after the leucine residue in the RxLxE/Q/D (or RxLxxE) motif of exported proteins including EMP1 (By similarity). Also, by regulating protein export, plays an essential role in gametocyte development and thus parasite transmission to the mosquito vector (By similarity).[UniProtKB:Q8I6Z5][UniProtKB:W7JPD9] Publication Abstract from PubMed Plasmepsin V, an essential aspartyl protease of malaria parasites, has a key role in the export of effector proteins to parasite-infected erythrocytes. Consequently, it is an important drug target for the two most virulent malaria parasites of humans, Plasmodium falciparum and Plasmodium vivax. We developed a potent inhibitor of plasmepsin V, called WEHI-842, which directly mimics the Plasmodium export element (PEXEL). WEHI-842 inhibits recombinant plasmepsin V with a half-maximal inhibitory concentration of 0.2 nM, efficiently blocks protein export and inhibits parasite growth. We obtained the structure of P. vivax plasmepsin V in complex with WEHI-842 to 2.4-A resolution, which provides an explanation for the strict requirements for substrate and inhibitor binding. The structure characterizes both a plant-like fold and a malaria-specific helix-turn-helix motif that are likely to be important in cleavage of effector substrates for export. Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes.,Hodder AN, Sleebs BE, Czabotar PE, Gazdik M, Xu Y, O'Neill MT, Lopaticki S, Nebl T, Triglia T, Smith BJ, Lowes K, Boddey JA, Cowman AF Nat Struct Mol Biol. 2015 Aug;22(8):590-6. doi: 10.1038/nsmb.3061. Epub 2015 Jul , 27. PMID:26214367 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Plasmepsin

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