View source for 3pnr


==Structure of PbICP-C in complex with falcipain-2==
<StructureSection load='3pnr' size='340' side='right'caption='[[3pnr]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pnr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_berghei Plasmodium berghei] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PNR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PNR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3pnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pnr OCA], [https://pdbe.org/3pnr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pnr RCSB], [https://www.ebi.ac.uk/pdbsum/3pnr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pnr ProSAT]</span></td></tr>
</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> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:21742259</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pnr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium berghei]]
[[Category: Plasmodium falciparum]]
[[Category: Hansen G]]
[[Category: Hilgenfeld R]]