4zt5
From Proteopedia
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==Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (2S)-N-(3,5-dichlorobenzyl)-N'-(1H-imidazo[4,5-b]pyridin-2-yl)-2-methylpropane-1,3-diamine (Chem 1655)== | ==Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (2S)-N-(3,5-dichlorobenzyl)-N'-(1H-imidazo[4,5-b]pyridin-2-yl)-2-methylpropane-1,3-diamine (Chem 1655)== | ||
| - | <StructureSection load='4zt5' size='340' side='right' caption='[[4zt5]], [[Resolution|resolution]] 2.35Å' scene=''> | + | <StructureSection load='4zt5' size='340' side='right'caption='[[4zt5]], [[Resolution|resolution]] 2.35Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4zt5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZT5 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4zt5]] 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=4ZT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZT5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4RN:(2S)-N-(3,5-DICHLOROBENZYL)-N-(1H-IMIDAZO[4,5-B]PYRIDIN-2-YL)-2-METHYLPROPANE-1,3-DIAMINE'>4RN</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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4RN:(2S)-N-(3,5-DICHLOROBENZYL)-N-(1H-IMIDAZO[4,5-B]PYRIDIN-2-YL)-2-METHYLPROPANE-1,3-DIAMINE'>4RN</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=4zt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zt5 OCA], [https://pdbe.org/4zt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zt5 RCSB], [https://www.ebi.ac.uk/pdbsum/4zt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zt5 ProSAT]</span></td></tr> | |
| - | + | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q38C91_TRYB2 Q38C91_TRYB2] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fluorination 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. | ||
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| + | 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<ref>PMID:27627628</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4zt5" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Trypanosoma brucei brucei TREU927]] |
| - | [[Category: | + | [[Category: Hol WGJ]] |
| - | [[Category: | + | [[Category: Koh C-Y]] |
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Current revision
Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (2S)-N-(3,5-dichlorobenzyl)-N'-(1H-imidazo[4,5-b]pyridin-2-yl)-2-methylpropane-1,3-diamine (Chem 1655)
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