7cty
From Proteopedia
(Difference between revisions)
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==Wild type plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), fragment 263, NADP+, dUMP== | ==Wild type plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), fragment 263, NADP+, dUMP== | ||
| - | <StructureSection load='7cty' size='340' side='right'caption='[[7cty]]' scene=''> | + | <StructureSection load='7cty' size='340' side='right'caption='[[7cty]], [[Resolution|resolution]] 2.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CTY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7cty]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CTY FirstGlance]. <br> |
| - | </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=7cty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cty OCA], [https://pdbe.org/7cty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cty RCSB], [https://www.ebi.ac.uk/pdbsum/7cty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cty ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GF3:spiro[1H-2-benzofuran-3,4-piperidine]'>GF3</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHFR-TS, dhfr-ts ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</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=7cty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cty OCA], [https://pdbe.org/7cty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cty RCSB], [https://www.ebi.ac.uk/pdbsum/7cty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cty ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/A7UD81_PLAFA A7UD81_PLAFA]] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism.[PIRNR:PIRNR000389] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In various malaria-endemic regions, the appearance of resistance has precluded the use of pyrimidine-based antifolate drugs. Here, a three-step fragment screening was used to identify new non-pyrimidine Plasmodium falciparum dihydrofolate reductase (PfDHFR) inhibitors. Starting from a 1163-fragment commercial library, a two-step differential scanning fluorimetry screen identified 75 primary fragment hits. Subsequent enzyme inhibition assay identified 11 fragments displaying IC50 in the 28-695 muM range and selectivity for PfDHFR. In addition to the known pyrimidine, three new anti-PfDHFR chemotypes were identified. Fragments from each chemotype were successfully co-crystallized with PfDHFR, revealing a binding in the active site, in the vicinity of catalytic residues, which was confirmed by molecular docking on all fragment hits. Finally, comparison with similar non-hit fragments provides preliminary input on available growth vectors for future drug development. | ||
| + | |||
| + | Discovery of new non-pyrimidine scaffolds as Plasmodium falciparum DHFR inhibitors by fragment-based screening.,Hoarau M, Vanichtanankul J, Srimongkolpithak N, Vitsupakorn D, Yuthavong Y, Kamchonwongpaisan S J Enzyme Inhib Med Chem. 2021 Dec;36(1):198-206. doi:, 10.1080/14756366.2020.1854244. PMID:33530764<ref>PMID:33530764</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7cty" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Vanichtanankul J]] | + | [[Category: Plafa]] |
| - | [[Category: Vitsupakorn D]] | + | [[Category: Vanichtanankul, J]] |
| + | [[Category: Vitsupakorn, D]] | ||
| + | [[Category: Antibiotic]] | ||
| + | [[Category: Antifolate]] | ||
| + | [[Category: Antimalarial]] | ||
| + | [[Category: Dihydrofolate reductase]] | ||
| + | [[Category: Fragment]] | ||
| + | [[Category: Oxidoreductase]] | ||
| + | [[Category: Plasmodium falciparum]] | ||
Revision as of 10:12, 7 July 2021
Wild type plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), fragment 263, NADP+, dUMP
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