4b1b: Difference between revisions
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==Crystal structure of Plasmodium falciparum oxidised Thioredoxin Reductase at 2.9 angstrom== | ==Crystal structure of Plasmodium falciparum oxidised Thioredoxin Reductase at 2.9 angstrom== | ||
<StructureSection load='4b1b' size='340' side='right' caption='[[4b1b]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='4b1b' size='340' side='right'caption='[[4b1b]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4b1b]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4b1b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B1B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B1B FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4b1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b1b OCA], [https://pdbe.org/4b1b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b1b RCSB], [https://www.ebi.ac.uk/pdbsum/4b1b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b1b ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/TRXR_PLAF7 TRXR_PLAF7] Catalyzes the transfer of electrons from NADPH to thioredoxins TRX1, TRX2 and TRX3, which in turn act as reductants of disulfide containing proteins (PubMed:9368022, PubMed:11013257, PubMed:16910770, PubMed:23845423). Able to reduce nitroglutathione (GSNO), a compound involved in the transport of nitric oxide (NO); however, TRX1 is more efficient in reducing GSNO (PubMed:11013257). Has no catalytic activity towards oxidized glutathione (GSSG) (PubMed:11013257).<ref>PMID:11013257</ref> <ref>PMID:16910770</ref> <ref>PMID:23845423</ref> <ref>PMID:9368022</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Thioredoxin | *[[Thioredoxin reductase 3D structures|Thioredoxin reductase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium falciparum]] | ||
[[Category: Angelucci | [[Category: Angelucci F]] | ||
[[Category: Bellelli | [[Category: Bellelli A]] | ||
[[Category: Boumis | [[Category: Boumis G]] | ||
[[Category: Brunori | [[Category: Brunori M]] | ||
[[Category: Dimastrogiovanni | [[Category: Dimastrogiovanni D]] | ||
[[Category: Giardina | [[Category: Giardina G]] | ||
[[Category: Miele | [[Category: Miele AE]] | ||
[[Category: Saccoccia | [[Category: Saccoccia F]] | ||
Latest revision as of 14:41, 20 December 2023
Crystal structure of Plasmodium falciparum oxidised Thioredoxin Reductase at 2.9 angstromCrystal structure of Plasmodium falciparum oxidised Thioredoxin Reductase at 2.9 angstrom
Structural highlights
FunctionTRXR_PLAF7 Catalyzes the transfer of electrons from NADPH to thioredoxins TRX1, TRX2 and TRX3, which in turn act as reductants of disulfide containing proteins (PubMed:9368022, PubMed:11013257, PubMed:16910770, PubMed:23845423). Able to reduce nitroglutathione (GSNO), a compound involved in the transport of nitric oxide (NO); however, TRX1 is more efficient in reducing GSNO (PubMed:11013257). Has no catalytic activity towards oxidized glutathione (GSSG) (PubMed:11013257).[1] [2] [3] [4] Publication Abstract from PubMedPlasmodium falciparum is the vector of the most prevalent and deadly form of malaria, and, among the Plasmodium species, it is the one with the highest rate of drug resistance. At the basis of a rational drug design project there is the selection and characterization of suitable target(s). Thioredoxin reductase, the first protection against reactive oxygen species in the erythrocytic phase of the parasite, is essential for its survival. Hence it represents a good target for the design of new anti-malarial active compounds. In this paper we present the first crystal structure of recombinant P. falciparum thioredoxin reductase (PfTrxR) at 2.9A and discuss its differences with respect to the human orthologue. The most important one resides in the dimer interface, which offers a good binding site for selective non competitive inhibitors. The striking conservation of this feature among the Plasmodium parasites, but not among other Apicomplexa parasites neither in mammals, boosts its exploitability. Crystal structure of Plasmodium falciparum thioredoxin reductase, a validated drug target.,Boumis G, Giardina G, Angelucci F, Bellelli A, Brunori M, Dimastrogiovanni D, Saccoccia F, Miele AE Biochem Biophys Res Commun. 2012 Aug 6. PMID:22889878[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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