6hl7: Difference between revisions
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<StructureSection load='6hl7' size='340' side='right'caption='[[6hl7]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='6hl7' size='340' side='right'caption='[[6hl7]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6hl7]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HL7 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[6hl7]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HL7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6HL7 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CP:PHOSPHORIC+ACID+MONO(FORMAMIDE)ESTER'>CP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CP:PHOSPHORIC+ACID+MONO(FORMAMIDE)ESTER'>CP</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATCase ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATCase ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase Aspartate carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.2 2.1.3.2] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase Aspartate carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.2 2.1.3.2] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6hl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl7 OCA], [http://pdbe.org/6hl7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hl7 RCSB], [http://www.ebi.ac.uk/pdbsum/6hl7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hl7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
Revision as of 08:56, 20 May 2020
Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum with mutated active site (R109A/K138A) and N-carbamoyl-L-phosphate boundCrystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum with mutated active site (R109A/K138A) and N-carbamoyl-L-phosphate bound
Structural highlights
Publication Abstract from PubMedMalaria is a tropical disease that kills about half a million people around the world annually. Enzymatic reactions within pyrimidine biosynthesis have been proven to be essential for Plasmodium proliferation. Here we report on the essentiality of the second enzymatic step of the pyrimidine biosynthesis pathway, catalyzed by aspartate transcarbamoylase (ATC). Crystallization experiments using a double mutant ofPlasmodium falciparum ATC (PfATC) revealed the importance of the mutated residues for enzyme catalysis. Subsequently, this mutant was employed in protein interference assays (PIAs), which resulted in inhibition of parasite proliferation when parasites transfected with the double mutant were cultivated in medium lacking an excess of nutrients, including aspartate. Addition of 5 or 10 mg/L of aspartate to the minimal medium restored the parasites' normal growth rate. In vitro and whole-cell assays in the presence of the compound Torin 2 showed inhibition of specific activity and parasite growth, respectively. In silico analyses revealed the potential binding mode of Torin 2 to PfATC. Furthermore, a transgenic ATC-overexpressing cell line exhibited a 10-fold increased tolerance to Torin 2 compared with control cultures. Taken together, our results confirm the antimalarial activity of Torin 2, suggesting PfATC as a target of this drug and a promising target for the development of novel antimalarials. Molecular Target Validation of Aspartate Transcarbamoylase from Plasmodium falciparum by Torin 2.,Bosch SS, Lunev S, Batista FA, Linzke M, Kronenberger T, Domling ASS, Groves MR, Wrenger C ACS Infect Dis. 2020 Mar 12. doi: 10.1021/acsinfecdis.9b00411. PMID:32129597[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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