4zt2: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4zt2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZT2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4zt2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZT2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4RP:N-(3,5-DICHLOROBENZYL)-N-(1H-IMIDAZO[4,5-B]PYRIDIN-2-YL)PROPANE-1,3-DIAMINE'>4RP</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4RP:N-(3,5-DICHLOROBENZYL)-N-(1H-IMIDAZO[4,5-B]PYRIDIN-2-YL)PROPANE-1,3-DIAMINE'>4RP</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4zt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zt2 OCA], [https://pdbe.org/4zt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zt2 RCSB], [https://www.ebi.ac.uk/pdbsum/4zt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zt2 ProSAT]</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=4zt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zt2 OCA], [https://pdbe.org/4zt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zt2 RCSB], [https://www.ebi.ac.uk/pdbsum/4zt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zt2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 11:23, 27 September 2023
Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor N-(3,5-dichlorobenzyl)-N'-(1H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine (Chem 1575)Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor N-(3,5-dichlorobenzyl)-N'-(1H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine (Chem 1575)
Structural highlights
FunctionPublication Abstract from PubMedFluorination is a well-known strategy for improving the bioavailability of drug molecules. However, its impact on efficacy is not easily predicted. On the basis of inhibitor-bound protein crystal structures, we found a beneficial fluorination spot for inhibitors targeting methionyl-tRNA synthetase of Trypanosoma brucei. In particular, incorporating 5-fluoroimidazo[4,5-b]pyridine into inhibitors leads to central nervous system bioavailability and maintained or even improved efficacy. 5-Fluoroimidazo[4,5-b]pyridine Is a Privileged Fragment That Conveys Bioavailability to Potent Trypanosomal Methionyl-tRNA Synthetase Inhibitors.,Zhang Z, Koh CY, Ranade RM, Shibata S, Gillespie JR, Hulverson MA, Huang W, Nguyen J, Pendem N, Gelb MH, Verlinde CL, Hol WG, Buckner FS, Fan E ACS Infect Dis. 2016 Jun 10;2(6):399-404. doi: 10.1021/acsinfecdis.6b00036. Epub , 2016 Apr 11. PMID:27627628[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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