View source for 4j57

==Structure of Plasmodium falciparum thioredoxin reductase-thioredoxin complex==
<StructureSection load='4j57' size='340' side='right' caption='[[4j57]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4j57]] is a 4 chain structure with sequence from [http://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=4J57 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J57 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">trxr2, PFI1170c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 Plasmodium falciparum 3D7]), PF14_0545 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 Plasmodium falciparum 3D7])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thioredoxin-disulfide_reductase Thioredoxin-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.9 1.8.1.9] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j57 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j57 RCSB], [http://www.ebi.ac.uk/pdbsum/4j57 PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Over the last decades, malaria parasites have been rapidly developing resistance against antimalarial drugs, which underlines the need for novel drug targets. Thioredoxin reductase (TrxR) is crucially involved in redox homeostasis and essential for Plasmodium falciparum. Here, we report the first crystal structure of P. falciparum TrxR bound to its substrate thioredoxin 1. Upon complex formation, the flexible C-terminal arm and an insertion loop of PfTrxR are rearranged, suggesting that the C-terminal arm changes its conformation during catalysis similar to human TrxR. Striking differences between P. falciparum and human TrxR are a Plasmodium-specific insertion and the conformation of the C-terminal arm, which lead to considerable differences in thioredoxin binding and disulfide reduction. Moreover, we functionally analyzed amino acid residues involved in substrate binding and in the architecture of the intersubunit cavity, which is a known binding site for disulfide reductase inhibitors. Cell biological experiments indicate that P. falciparum TrxR is indeed targeted in the parasite by specific inhibitors with antimalarial activity. Differences between P. falciparum and human TrxR and details on substrate reduction and inhibitor binding provide the first solid basis for structure-based drug development and lead optimization.

Crystal Structure of the Plasmodium falciparum Thioredoxin Reductase-Thioredoxin Complex.,Fritz-Wolf K, Jortzik E, Stumpf M, Preuss J, Iozef R, Rahlfs S, Becker K J Mol Biol. 2013 Jul 9. pii: S0022-2836(13)00432-4. doi:, 10.1016/j.jmb.2013.06.037. PMID:23845423<ref>PMID:23845423</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Thioredoxin|Thioredoxin]]
*[[Thioredoxin Reductase|Thioredoxin Reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Plasmodium falciparum 3d7]]
[[Category: Thioredoxin-disulfide reductase]]
[[Category: Becker, K]]
[[Category: Fritz-Wolf, K]]
[[Category: Iozef, R]]
[[Category: Jortzik, E]]
[[Category: Preuss, J]]
[[Category: Rahlfs, S]]
[[Category: Stumpf, M]]
[[Category: Disulfide reductase]]
[[Category: Fad binding]]
[[Category: Nadph binding]]
[[Category: Oxidoreductase]]
[[Category: Protein-protein complex]]
[[Category: Thioredoxin binding]]
[[Category: Thioredoxin fold]]