4o32: Difference between revisions
New page: '''Unreleased structure''' The entry 4o32 is ON HOLD Authors: Egea, P.F., Koehl, A., Peng, M., Cascio, D. Description: Structure of a malarial protein |
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The | ==Structure of a malarial protein== | ||
<StructureSection load='4o32' size='340' side='right'caption='[[4o32]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4o32]] is a 3 chain structure with sequence from [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=4O32 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O32 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]] 2.196Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=4o32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o32 OCA], [https://pdbe.org/4o32 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o32 RCSB], [https://www.ebi.ac.uk/pdbsum/4o32 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o32 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/THIO2_PLAF7 THIO2_PLAF7] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:16910770, PubMed:22355694). As part of the translocon PTEX complex, plays a role in the export of parasite proteins into the host erythrocyte (By similarity). The translocon PTEX complex is a multi-protein machinery resident in the parasite parasitophorous vacuolar membrane, responsible for protein secretion into host cells (PubMed:19536257). May contribute to the unfolding of proteins containing the PEXEL localization motif before their passage through the translocon or regulate the PTEX complex function (PubMed:19536257).[UniProtKB:A0A509AQW5]<ref>PMID:16910770</ref> <ref>PMID:19536257</ref> <ref>PMID:22355694</ref> <ref>PMID:19536257</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Survival of the malaria parasite Plasmodium falciparum when it infects red blood cells depends upon its ability to export hundreds of its proteins beyond an encasing vacuole. Protein export is mediated by a parasite-derived protein complex, the Plasmodium translocon of exported proteins (PTEX), and requires unfolding of the different cargos prior to their translocation across the vacuolar membrane. Unfolding is performed by the AAA+protein unfoldase HSP101/ClpB2 and the thioredoxin-2 enzyme (TRX2). Protein trafficking is dramatically impaired in parasites with defective HSP101 or lacking TRX2. These two PTEX subunits drive export and are targets for the design of a novel class of antimalarials: protein export inhibitors. To rationalize inhibitor design, we solved the crystal structure of Pfal-TRX2 at 2.2-A resolution. Within the asymmetric unit, the three different copies of this protein disulfide reductase sample its two redox catalytic states. Size exclusion chromatography and small-angle X-ray scattering (SAXS) analyses demonstrate that Pfal-TRX2 is monomeric in solution. A non-conserved N-terminal extension precedes the canonical thioredoxin-fold; although it is not observed in our structure, our solution analysis suggests it is flexible in contrast to Plasmodium thioredoxin-1. This represents a first step towards the reconstitution of the entire PTEX for mechanistic and structural studies. | |||
Crystal structure and solution characterization of the thioredoxin-2 from Plasmodium falciparum, a constituent of an essential parasitic protein export complex.,Peng M, Cascio D, Egea PF Biochem Biophys Res Commun. 2014 Dec 2. pii: S0006-291X(14)02137-8. doi:, 10.1016/j.bbrc.2014.11.096. PMID:25475729<ref>PMID:25475729</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4o32" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thioredoxin 3D structures|Thioredoxin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum 3D7]] | |||
[[Category: Cascio D]] | |||
[[Category: Egea PF]] | |||
[[Category: Koehl A]] | |||
[[Category: Peng M]] | |||
Latest revision as of 14:13, 6 November 2024
Structure of a malarial proteinStructure of a malarial protein
Structural highlights
FunctionTHIO2_PLAF7 Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:16910770, PubMed:22355694). As part of the translocon PTEX complex, plays a role in the export of parasite proteins into the host erythrocyte (By similarity). The translocon PTEX complex is a multi-protein machinery resident in the parasite parasitophorous vacuolar membrane, responsible for protein secretion into host cells (PubMed:19536257). May contribute to the unfolding of proteins containing the PEXEL localization motif before their passage through the translocon or regulate the PTEX complex function (PubMed:19536257).[UniProtKB:A0A509AQW5][1] [2] [3] [4] Publication Abstract from PubMedSurvival of the malaria parasite Plasmodium falciparum when it infects red blood cells depends upon its ability to export hundreds of its proteins beyond an encasing vacuole. Protein export is mediated by a parasite-derived protein complex, the Plasmodium translocon of exported proteins (PTEX), and requires unfolding of the different cargos prior to their translocation across the vacuolar membrane. Unfolding is performed by the AAA+protein unfoldase HSP101/ClpB2 and the thioredoxin-2 enzyme (TRX2). Protein trafficking is dramatically impaired in parasites with defective HSP101 or lacking TRX2. These two PTEX subunits drive export and are targets for the design of a novel class of antimalarials: protein export inhibitors. To rationalize inhibitor design, we solved the crystal structure of Pfal-TRX2 at 2.2-A resolution. Within the asymmetric unit, the three different copies of this protein disulfide reductase sample its two redox catalytic states. Size exclusion chromatography and small-angle X-ray scattering (SAXS) analyses demonstrate that Pfal-TRX2 is monomeric in solution. A non-conserved N-terminal extension precedes the canonical thioredoxin-fold; although it is not observed in our structure, our solution analysis suggests it is flexible in contrast to Plasmodium thioredoxin-1. This represents a first step towards the reconstitution of the entire PTEX for mechanistic and structural studies. Crystal structure and solution characterization of the thioredoxin-2 from Plasmodium falciparum, a constituent of an essential parasitic protein export complex.,Peng M, Cascio D, Egea PF Biochem Biophys Res Commun. 2014 Dec 2. pii: S0006-291X(14)02137-8. doi:, 10.1016/j.bbrc.2014.11.096. PMID:25475729[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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