3pnr

Structure of PbICP-C in complex with falcipain-2

spinqualitylabelsall models 3pnr, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3pnr is a 2 chain structure with sequence from Plasmodium berghei and Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: CD, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FPC2A_PLAF7 Cysteine protease which cleaves native host hemoglobin and globin in the food vacuole during the asexual blood stage (PubMed:10887194, PubMed:15070727, PubMed:15964982, PubMed:16777845, PubMed:19357776, PubMed:25791019). The binding to host hemoglobin is pH-sensitive and only occurs at acidic pH (PubMed:16777845). Cleaves ankyrin and protein 4.1, two components of host erythrocyte membrane cytoskeleton required for the stability of the erythrocyte membrane, and thus may be involved in parasite release (PubMed:11463472). Preferentially cleaves substrates which have an arginine or lysine at the P1 position and a leucine or phenylalanine at the P2 position (PubMed:10887194, PubMed:19357776). Publication Abstract from PubMed Plasmodium cysteine proteases are essential for host-cell invasion and egress, hemoglobin degradation, and intracellular development of the parasite. The temporal, site-specific regulation of cysteine-protease activity is a prerequisite for survival and propagation of Plasmodium. Recently, a new family of inhibitors of cysteine proteases (ICPs) with homologs in at least eight Plasmodium species has been identified. Here, we report the 2.6 A X-ray crystal structure of the C-terminal, inhibitory domain of ICP from P. berghei (PbICP-C) in a 1:1 complex with falcipain-2, an important hemoglobinase of Plasmodium. The structure establishes Plasmodium ICP as a member of the I42 class of chagasin-like protease inhibitors but with large insertions and differences in the binding mode relative to other family members. Furthermore, the PbICP-C structure explains why host-cell cathepsin B-like proteases and, most likely, also the protease-like domain of Plasmodium SERA5 (serine-repeat antigen 5) are no targets for ICP. Structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in Plasmodium.,Hansen G, Heitmann A, Witt T, Li H, Jiang H, Shen X, Heussler VT, Rennenberg A, Hilgenfeld R Structure. 2011 Jul 13;19(7):919-29. PMID:21742259 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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