View source for 4j56


==Structure of Plasmodium falciparum thioredoxin reductase-thioredoxin complex==
<StructureSection load='4j56' size='340' side='right' caption='[[4j56]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4j56]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J56 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J56 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></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 PLAF7]), PF14_0545 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=4j56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j56 OCA], [http://pdbe.org/4j56 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j56 RCSB], [http://www.ebi.ac.uk/pdbsum/4j56 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j56 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/THIO_PLAF7 THIO_PLAF7]] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (By similarity). 
<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>
<div class="pdbe-citations 4j56" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thioredoxin|Thioredoxin]]
*[[Thioredoxin Reductase|Thioredoxin Reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Plaf7]]
[[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]]