7ry7: Difference between revisions
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==Structure of Plasmepsin X (PM10, PMX) from Plasmodium falciparum 3D7== | ==Structure of Plasmepsin X (PM10, PMX) from Plasmodium falciparum 3D7== | ||
<StructureSection load='7ry7' size='340' side='right'caption='[[7ry7]]' scene=''> | <StructureSection load='7ry7' size='340' side='right'caption='[[7ry7]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6ors 6ors]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RY7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ry7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6ors 6ors]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RY7 FirstGlance]. <br> | ||
</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=7ry7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ry7 OCA], [https://pdbe.org/7ry7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ry7 RCSB], [https://www.ebi.ac.uk/pdbsum/7ry7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ry7 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7ry7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ry7 OCA], [https://pdbe.org/7ry7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ry7 RCSB], [https://www.ebi.ac.uk/pdbsum/7ry7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ry7 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/PLM10_PLAF7 PLM10_PLAF7] During the asexual blood stage, processes key proteins essential for merozoite egress and invasion of host erythrocytes (PubMed:29074775, PubMed:32109369). Cleaves and activates proteases SUB1 and SUB2 (PubMed:29074775, PubMed:32109369). May process members of the EBL and Rh protein families (PubMed:32109369). Also cleaves apical membrane protein AMA1 (PubMed:29074775). During the mosquito vector stage and probably in ookinetes, cleaves CelTOS (PubMed:29074775).<ref>PMID:29074775</ref> <ref>PMID:32109369</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Plasmodium falciparum plasmepsin X (PfPMX), involved in the invasion and egress of this deadliest malarial parasite, is essential for its survival and hence considered as an important drug target. We report the first crystal structure of PfPMX zymogen containing a novel fold of its prosegment. A unique twisted loop from the prosegment and arginine 244 from the mature enzyme are involved in zymogen inactivation; such mechanism, not previously reported, might be common for apicomplexan proteases similar to PfPMX. The maturation of PfPMX zymogen occurs through cleavage of its prosegment at multiple sites. Our data provide thorough insights into the mode of binding of a substrate and a potent inhibitor 49c to PfPMX. We present molecular details of inactivation, maturation, and inhibition of PfPMX that should aid in the development of potent inhibitors against pepsin-like aspartic proteases from apicomplexan parasites. This article is protected by copyright. All rights reserved. | |||
Structures of plasmepsin X from P. falciparum reveal a novel inactivation mechanism of the zymogen and molecular basis for binding of inhibitors in mature enzyme.,Kesari P, Deshmukh A, Pahelkar N, Suryawanshi AB, Rathore I, Mishra V, Dupuis JH, Xiao H, Gustchina A, Abendroth J, Labaied M, Yada RY, Wlodawer A, Edwards TE, Lorimer DD, Bhaumik P Protein Sci. 2022 Jan 20. doi: 10.1002/pro.4279. PMID:35048450<ref>PMID:35048450</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ry7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Plasmepsin|Plasmepsin]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Plasmodium falciparum 3D7]] | |||
Latest revision as of 19:40, 18 October 2023
Structure of Plasmepsin X (PM10, PMX) from Plasmodium falciparum 3D7Structure of Plasmepsin X (PM10, PMX) from Plasmodium falciparum 3D7
Structural highlights
FunctionPLM10_PLAF7 During the asexual blood stage, processes key proteins essential for merozoite egress and invasion of host erythrocytes (PubMed:29074775, PubMed:32109369). Cleaves and activates proteases SUB1 and SUB2 (PubMed:29074775, PubMed:32109369). May process members of the EBL and Rh protein families (PubMed:32109369). Also cleaves apical membrane protein AMA1 (PubMed:29074775). During the mosquito vector stage and probably in ookinetes, cleaves CelTOS (PubMed:29074775).[1] [2] Publication Abstract from PubMedPlasmodium falciparum plasmepsin X (PfPMX), involved in the invasion and egress of this deadliest malarial parasite, is essential for its survival and hence considered as an important drug target. We report the first crystal structure of PfPMX zymogen containing a novel fold of its prosegment. A unique twisted loop from the prosegment and arginine 244 from the mature enzyme are involved in zymogen inactivation; such mechanism, not previously reported, might be common for apicomplexan proteases similar to PfPMX. The maturation of PfPMX zymogen occurs through cleavage of its prosegment at multiple sites. Our data provide thorough insights into the mode of binding of a substrate and a potent inhibitor 49c to PfPMX. We present molecular details of inactivation, maturation, and inhibition of PfPMX that should aid in the development of potent inhibitors against pepsin-like aspartic proteases from apicomplexan parasites. This article is protected by copyright. All rights reserved. Structures of plasmepsin X from P. falciparum reveal a novel inactivation mechanism of the zymogen and molecular basis for binding of inhibitors in mature enzyme.,Kesari P, Deshmukh A, Pahelkar N, Suryawanshi AB, Rathore I, Mishra V, Dupuis JH, Xiao H, Gustchina A, Abendroth J, Labaied M, Yada RY, Wlodawer A, Edwards TE, Lorimer DD, Bhaumik P Protein Sci. 2022 Jan 20. doi: 10.1002/pro.4279. PMID:35048450[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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