| Structural highlights
8gt0 is a 5 chain structure with sequence from Homo sapiens 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 3.28Å |
| Ligands: | , , , , , , , |
| 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).[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Shenai BR, Sijwali PS, Singh A, Rosenthal PJ. Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J Biol Chem. 2000 Sep 15;275(37):29000-10. PMID:10887194 doi:10.1074/jbc.M004459200
- ↑ Dua M, Raphael P, Sijwali PS, Rosenthal PJ, Hanspal M. Recombinant falcipain-2 cleaves erythrocyte membrane ankyrin and protein 4.1. Mol Biochem Parasitol. 2001 Aug;116(1):95-9. PMID:11463472 doi:10.1016/s0166-6851(01)00306-1
- ↑ Sijwali PS, Rosenthal PJ. Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4384-9. PMID:15070727 doi:10.1073/pnas.0307720101
- ↑ Pandey KC, Wang SX, Sijwali PS, Lau AL, McKerrow JH, Rosenthal PJ. The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif. Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9138-43. PMID:15964982 doi:10.1073/pnas.0502368102
- ↑ Hogg T, Nagarajan K, Herzberg S, Chen L, Shen X, Jiang H, Wecke M, Blohmke C, Hilgenfeld R, Schmidt CL. Structural and functional characterization of Falcipain-2, a hemoglobinase from the malarial parasite Plasmodium falciparum. J Biol Chem. 2006 Sep 1;281(35):25425-37. Epub 2006 Jun 15. PMID:16777845 doi:10.1074/jbc.M603776200
- ↑ Subramanian S, Hardt M, Choe Y, Niles RK, Johansen EB, Legac J, Gut J, Kerr ID, Craik CS, Rosenthal PJ. Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3. PLoS One. 2009;4(4):e5156. PMID:19357776 doi:10.1371/journal.pone.0005156
- ↑ Marques AF, Gomes PS, Oliveira PL, Rosenthal PJ, Pascutti PG, Lima LM. Allosteric regulation of the Plasmodium falciparum cysteine protease falcipain-2 by heme. Arch Biochem Biophys. 2015 May 1;573:92-9. PMID:25791019 doi:10.1016/j.abb.2015.03.007
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