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| | <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 with sequence from [http://en.wikipedia.org/wiki/Tryb2 Tryb2]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZT5 FirstGlance]. <br> | + | <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> | + | </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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zt7|4zt7]], [[4zt6|4zt6]], [[4zt4|4zt4]], [[4zt3|4zt3]], [[4zt2|4zt2]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tb10.70.6470 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=185431 TRYB2])</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=4zt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zt5 OCA], [http://pdbe.org/4zt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zt5 RCSB], [http://www.ebi.ac.uk/pdbsum/4zt5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zt5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q38C91_TRYB2 Q38C91_TRYB2] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Methionine--tRNA ligase]] | + | [[Category: Trypanosoma brucei brucei TREU927]] |
| - | [[Category: Tryb2]]
| + | [[Category: Hol WGJ]] |
| - | [[Category: Hol, W G.J]] | + | [[Category: Koh C-Y]] |
| - | [[Category: Koh, C Y]] | + | |
| - | [[Category: Aar]]
| + | |
| - | [[Category: Aminoacyl-trna synthetase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Ligase-ligase inhibitor complex]]
| + | |
| - | [[Category: Metr]]
| + | |
| - | [[Category: Protein-inhibitor complex]]
| + | |
| - | [[Category: Trypanosoma brucei]]
| + | |
| Structural highlights
4zt5 is a 2 chain structure with sequence from Trypanosoma brucei brucei TREU927. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q38C91_TRYB2
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.
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 Also
References
- ↑ 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. 5-Fluoroimidazo[4,5-b]pyridine Is a Privileged Fragment That Conveys Bioavailability to Potent Trypanosomal Methionyl-tRNA Synthetase Inhibitors. ACS Infect Dis. 2016 Jun 10;2(6):399-404. doi: 10.1021/acsinfecdis.6b00036. Epub , 2016 Apr 11. PMID:27627628 doi:http://dx.doi.org/10.1021/acsinfecdis.6b00036
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