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| | <StructureSection load='5jld' size='340' side='right'caption='[[5jld]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='5jld' size='340' side='right'caption='[[5jld]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jld]] is a 1 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=5JLD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JLD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jld]] is a 1 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=5JLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JLD FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFL0900c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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]] 2.2Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Arginine--tRNA_ligase Arginine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.19 6.1.1.19] </span></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=5jld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jld OCA], [https://pdbe.org/5jld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jld RCSB], [https://www.ebi.ac.uk/pdbsum/5jld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jld ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jld OCA], [http://pdbe.org/5jld PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jld RCSB], [http://www.ebi.ac.uk/pdbsum/5jld PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jld ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q8I5M2_PLAF7 Q8I5M2_PLAF7] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arginine--tRNA ligase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plaf7]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Jain, V]] | + | [[Category: Jain V]] |
| - | [[Category: Manickam, Y]] | + | [[Category: Manickam Y]] |
| - | [[Category: Sharma, A]] | + | [[Category: Sharma A]] |
| - | [[Category: Arginyl-trna synthetase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Malaria]]
| + | |
| - | [[Category: Translation]]
| + | |
| Structural highlights
Function
Q8I5M2_PLAF7
Publication Abstract from PubMed
Excess cellular heme is toxic, and malaria parasites regulate its levels during hemoglobin digestion. Aminoacyl-tRNA synthetases are ubiquitous enzymes, and of these, arginyl-tRNA synthetase (RRS) is unique as its enzymatic product of charged tRNA is required for protein synthesis and degradation. We show that Plasmodium falciparum arginyl-tRNA synthetase (PfRRS) is an active, cytosolic, and monomeric enzyme. Its high-resolution crystal structure highlights critical structural differences with the human enzyme. We further show that hemin binds to and inhibits the aminoacylation activity of PfRRS. Hemin induces a dimeric form of PfRRS that is thus rendered enzymatically dead as it is unable to recognize its cognate tRNAarg. Excessive hemin in chloroquine-treated malaria parasites results in significantly reduced charged tRNAarg levels, thus suggesting deceleration of protein synthesis. These data together suggest that the inhibition of Plasmodium falciparum arginyl-tRNA synthetase can now be synergized with existing antimalarials for more potent drug cocktails against malaria parasites.
Dimerization of Arginyl-tRNA Synthetase by Free Heme Drives Its Inactivation in Plasmodium falciparum.,Jain V, Yogavel M, Sharma A Structure. 2016 Sep 6;24(9):1476-1487. doi: 10.1016/j.str.2016.06.018. Epub 2016 , Aug 5. PMID:27502052[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jain V, Yogavel M, Sharma A. Dimerization of Arginyl-tRNA Synthetase by Free Heme Drives Its Inactivation in Plasmodium falciparum. Structure. 2016 Sep 6;24(9):1476-1487. doi: 10.1016/j.str.2016.06.018. Epub 2016 , Aug 5. PMID:27502052 doi:http://dx.doi.org/10.1016/j.str.2016.06.018
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