4pg3: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4pg3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PG3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4pg3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PG3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KRS: | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KRS:CLADOSPORIN'>KRS</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pg3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pg3 RCSB], [http://www.ebi.ac.uk/pdbsum/4pg3 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pg3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pg3 RCSB], [http://www.ebi.ac.uk/pdbsum/4pg3 PDBsum]</span></td></tr> | ||
Revision as of 10:14, 26 March 2015
Crystal structure of KRS complexed with inhibitorCrystal structure of KRS complexed with inhibitor
Structural highlights
Publication Abstract from PubMedMalaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin's remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase. Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin.,Khan S, Sharma A, Belrhali H, Yogavel M, Sharma A J Struct Funct Genomics. 2014 Jun;15(2):63-71. doi: 10.1007/s10969-014-9182-1., Epub 2014 Jun 17. PMID:24935905[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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