6m0t
From Proteopedia
(Difference between revisions)
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==Crystal Structure of Lysyl-tRNA Synthetase from Plasmodium falciparum complexed with L-lysine and Cladosporin derivative (CL-2)== | ==Crystal Structure of Lysyl-tRNA Synthetase from Plasmodium falciparum complexed with L-lysine and Cladosporin derivative (CL-2)== | ||
| - | <StructureSection load='6m0t' size='340' side='right'caption='[[6m0t]]' scene=''> | + | <StructureSection load='6m0t' size='340' side='right'caption='[[6m0t]], [[Resolution|resolution]] 2.68Å' 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=6M0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M0T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6m0t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M0T 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=6m0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m0t OCA], [https://pdbe.org/6m0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m0t RCSB], [https://www.ebi.ac.uk/pdbsum/6m0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m0t 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=EZ3:(3R)-3-[(R)-[(2R,6S)-6-methyloxan-2-yl]-oxidanyl-methyl]-6,8-bis(oxidanyl)-3,4-dihydroisochromen-1-one'>EZ3</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4pg3|4pg3]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF3D7_1350100 ([https://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'>[https://en.wikipedia.org/wiki/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] </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=6m0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m0t OCA], [https://pdbe.org/6m0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m0t RCSB], [https://www.ebi.ac.uk/pdbsum/6m0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m0t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from cladosporin, a tool compound that targets parasite (Plasmodium falciparum) lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with in vitro pharmacokinetics. Co-crystallization of the most potent compound in our series (CL-2) with PfKRS revealed its structural basis of enzymatic binding and potency. Further, we report that CL-2 has performed better than cladosporin in terms of metabolic stability. It thus represents a new lead for further optimization toward the development of antimalarial drugs. Collectively, along with a lead compound, the series offers insights on how even the slightest chemical modification might play an important role in enhancing or decreasing the potency of a chemical scaffold. | ||
| + | |||
| + | Design, Synthesis, and Structural Analysis of Cladosporin-Based Inhibitors of Malaria Parasites.,Babbar P, Das P, Manickam Y, Mankad Y, Yadav S, Parvez S, Sharma A, Reddy DS ACS Infect Dis. 2021 Apr 12. doi: 10.1021/acsinfecdis.1c00092. PMID:33843204<ref>PMID:33843204</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6m0t" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Babbar P]] | + | [[Category: Lysine--tRNA ligase]] |
| - | [[Category: Manickam Y]] | + | [[Category: Plaf7]] |
| - | [[Category: Sharma A]] | + | [[Category: Babbar, P]] |
| + | [[Category: Manickam, Y]] | ||
| + | [[Category: Sharma, A]] | ||
| + | [[Category: Cladosporin analog]] | ||
| + | [[Category: Ligase-ligase inhibitor complex]] | ||
| + | [[Category: Stereochemistry]] | ||
Revision as of 07:41, 25 June 2021
Crystal Structure of Lysyl-tRNA Synthetase from Plasmodium falciparum complexed with L-lysine and Cladosporin derivative (CL-2)
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