6fba
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==Crystal Structure of truncated aspartate transcarbamoylase from Plasmodium falciparum with bound inhibitor 2,3-naphthalenediol== | ==Crystal Structure of truncated aspartate transcarbamoylase from Plasmodium falciparum with bound inhibitor 2,3-naphthalenediol== | ||
| - | <StructureSection load='6fba' size='340' side='right' caption='[[6fba]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='6fba' size='340' side='right'caption='[[6fba]], [[Resolution|resolution]] 2.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6fba]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FBA OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6fba]] is a 3 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=6FBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FBA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D48:naphthalene-2,3-diol'>D48</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=D48:naphthalene-2,3-diol'>D48</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6fba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fba OCA], [https://pdbe.org/6fba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fba RCSB], [https://www.ebi.ac.uk/pdbsum/6fba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fba ProSAT]</span></td></tr> | |
| - | + | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/O15804_PLAFA O15804_PLAFA] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Aspartate transcarbamoylase catalyzes the second step of de-novo pyrimidine biosynthesis. As malarial parasites lack pyrimidine salvage machinery and rely on de-novo production for growth and proliferation, this pathway is a target for drug discovery. Previously, an apo crystal structure of aspartate transcarbamoylase from Plasmodium falciparum (PfATC) in its T-state has been reported. Here we present crystal structures of PfATC in the liganded R-state as well as in complex with the novel inhibitor, 2,3-napthalenediol, identified by high-throughput screening. Our data shows that 2,3-napthalediol binds in close proximity to the active site, implying an allosteric mechanism of inhibition. Furthermore, we report biophysical characterization of 2,3-napthalenediol. These data provide a promising starting point for structure based drug design targeting PfATC and malarial de-novo pyrimidine biosynthesis. | ||
| + | |||
| + | Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase.,Lunev S, Bosch SS, Batista FA, Wang C, Li J, Linzke M, Kruithof P, Chamoun G, Domling ASS, Wrenger C, Groves MR Biochem Biophys Res Commun. 2018 Mar 11;497(3):835-842. doi:, 10.1016/j.bbrc.2018.02.112. Epub 2018 Feb 21. PMID:29476738<ref>PMID:29476738</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6fba" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Aspartate carbamoyltransferase 3D structures|Aspartate carbamoyltransferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Batista | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Bosch | + | [[Category: Batista FA]] |
| - | [[Category: Groves | + | [[Category: Bosch SS]] |
| - | [[Category: Lunev | + | [[Category: Groves MR]] |
| - | [[Category: Wang | + | [[Category: Lunev S]] |
| - | [[Category: Wrenger | + | [[Category: Wang C]] |
| - | + | [[Category: Wrenger C]] | |
| - | + | ||
Current revision
Crystal Structure of truncated aspartate transcarbamoylase from Plasmodium falciparum with bound inhibitor 2,3-naphthalenediol
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