5zh2: Difference between revisions
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<StructureSection load='5zh2' size='340' side='right' caption='[[5zh2]], [[Resolution|resolution]] 2.66Å' scene=''> | <StructureSection load='5zh2' size='340' side='right' caption='[[5zh2]], [[Resolution|resolution]] 2.66Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5zh2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZH2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5zh2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafo Plafo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZH2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9CU:(3R)-6,8-dihydroxy-3-{[(2R,6R)-6-methyloxan-2-yl]methyl}-3,4-dihydro-1H-2-benzopyran-1-one'>9CU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9CU:(3R)-6,8-dihydroxy-3-{[(2R,6R)-6-methyloxan-2-yl]methyl}-3,4-dihydro-1H-2-benzopyran-1-one'>9CU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFNF54_04763 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5843 PLAFO])</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=5zh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zh2 OCA], [http://pdbe.org/5zh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zh2 RCSB], [http://www.ebi.ac.uk/pdbsum/5zh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zh2 ProSAT]</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=5zh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zh2 OCA], [http://pdbe.org/5zh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zh2 RCSB], [http://www.ebi.ac.uk/pdbsum/5zh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zh2 ProSAT]</span></td></tr> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Lysine--tRNA ligase]] | [[Category: Lysine--tRNA ligase]] | ||
[[Category: Plafo]] | |||
[[Category: Babbar, P]] | [[Category: Babbar, P]] | ||
[[Category: Harlos, K]] | [[Category: Harlos, K]] | ||
Revision as of 10:31, 25 July 2018
CRYSTAL STRUCTURE OF PfKRS WITH INHIBITOR CLADO-5CRYSTAL STRUCTURE OF PfKRS WITH INHIBITOR CLADO-5
Structural highlights
Publication Abstract from PubMedThe dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral center antimalarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme-, and structure-based assays. We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency whereas changes at C3 are sensed by rotameric flipping of glutamate 332. Given that scores of antimalarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of antimicrobial drug development. Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite.,Das P, Babbar P, Malhotra N, Sharma M, Jachak GR, Gonnade RG, Shanmugam D, Harlos K, Yogavel M, Sharma A, Reddy DS J Med Chem. 2018 Jun 4. doi: 10.1021/acs.jmedchem.8b00565. PMID:29779382[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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