5j5a
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (Chem 70786556)== | |
| + | <StructureSection load='5j5a' size='340' side='right' caption='[[5j5a]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5j5a]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J5A FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=756:[(3S)-3-(1H-BENZIMIDAZOL-2-YL)PIPERIDIN-1-YL](2-METHYL-1-BENZOFURAN-5-YL)METHANONE'>756</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </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=5j5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5a OCA], [http://pdbe.org/5j5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j5a RCSB], [http://www.ebi.ac.uk/pdbsum/5j5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5a ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A screening hit 1 against Trypanosoma brucei methionyl-tRNA synthetase was optimized using a structure-guided approach. The optimization led to the identification of two novel series of potent inhibitors, the cyclic linker and linear linker series. Compounds of both series were potent in a T. brucei growth inhibition assay while showing low toxicity to mammalian cells. The best compound of each series, 16 and 31, exhibited EC50s of 39 and 22 nM, respectively. Compounds 16 and 31 also exhibited promising PK properties after oral dosing in mice. Moreover, compound 31 had moderately good brain permeability, with a brain/plasma ratio of 0.27 at 60 min after IP injection. This study provides new lead compounds for arriving at new treatments of human African trypanosomiasis (HAT). | ||
| - | + | Structure-guided design of novel Trypanosoma brucei Methionyl-tRNA synthetase inhibitors.,Huang W, Zhang Z, Barros-Alvarez X, Koh CY, Ranade RM, Gillespie JR, Creason SA, Shibata S, Verlinde CL, Hol WG, Buckner FS, Fan E Eur J Med Chem. 2016 Nov 29;124:1081-1092. doi: 10.1016/j.ejmech.2016.10.024., Epub 2016 Oct 14. PMID:27788467<ref>PMID:27788467</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5j5a" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Methionine--tRNA ligase]] | ||
[[Category: Barros-Alvarez, X]] | [[Category: Barros-Alvarez, X]] | ||
| - | [[Category: Koh, C | + | [[Category: Hol, W G.J]] |
| + | [[Category: Koh, C Y]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Ligase]] | ||
| + | [[Category: Ligase-ligase inhibitor complex]] | ||
| + | [[Category: Methionine]] | ||
| + | [[Category: Synthetase]] | ||
Revision as of 23:26, 25 January 2017
Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (Chem 70786556)
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