8gt7: Difference between revisions

Latest revision as of 05:59, 17 September 2025

Structure of falcipain and human Stefin A mutant complex

Structural highlights

8gt7 is a 6 chain structure with sequence from Homo sapiens and Plasmodium falciparum 3D7. 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:	EDO, GOL, NA, PE8, PEG, PG4, SO4
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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OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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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[3]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8gt7 is ON HOLD  until Paper Publication
+==Structure of falcipain and human Stefin A mutant complex==
+<StructureSection load='8gt7' size='340' side='right'caption='[[8gt7]], [[Resolution|resolution]] 3.28&Aring;' scene=''>
-Authors: Chakraborty, S., Biswas, S.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8gt7]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GT7 FirstGlance]. <br>
-Description: Structure of falcipain and human Stefin A mutant complex
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.28&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PE8:3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL'>PE8</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-[[Category: Chakraborty, S]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gt7 OCA], [https://pdbe.org/8gt7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gt7 RCSB], [https://www.ebi.ac.uk/pdbsum/8gt7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gt7 ProSAT]</span></td></tr>
-[[Category: Biswas, S]]
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/FPC2A_PLAF7 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).<ref>PMID:10887194</ref> <ref>PMID:11463472</ref> <ref>PMID:15070727</ref> <ref>PMID:15964982</ref> <ref>PMID:16777845</ref> <ref>PMID:19357776</ref> <ref>PMID:25791019</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Plasmodium falciparum 3D7]]
+[[Category: Biswas S]]
+[[Category: Chakraborty S]]

8gt7: Difference between revisions

Latest revision as of 05:59, 17 September 2025

Structure of falcipain and human Stefin A mutant complex

Structural highlights

Function

References

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