5v49

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:31, 6 March 2024) (edit) (undo)
 
Line 3: Line 3:
<StructureSection load='5v49' size='340' side='right'caption='[[5v49]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='5v49' size='340' side='right'caption='[[5v49]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[5v49]] 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=5V49 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V49 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[5v49]] 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=5V49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V49 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8WA:N~1~-(5-chloro-1H-imidazo[4,5-b]pyridin-2-yl)-N~2~-[(4R)-6,8-dichloro-1,2,3,4-tetrahydroquinolin-4-yl]-N~1~-methylethane-1,2-diamine'>8WA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</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]] 2.3&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8WA:N~1~-(5-chloro-1H-imidazo[4,5-b]pyridin-2-yl)-N~2~-[(4R)-6,8-dichloro-1,2,3,4-tetrahydroquinolin-4-yl]-N~1~-methylethane-1,2-diamine'>8WA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[https://proteopedia.org/fgij/fg.htm?mol=5v49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v49 OCA], [https://pdbe.org/5v49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v49 RCSB], [https://www.ebi.ac.uk/pdbsum/5v49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v49 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=5v49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v49 OCA], [http://pdbe.org/5v49 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v49 RCSB], [http://www.ebi.ac.uk/pdbsum/5v49 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v49 ProSAT]</span></td></tr>
+
</table>
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[https://www.uniprot.org/uniprot/Q38C91_TRYB2 Q38C91_TRYB2]
-
Potent inhibitors of Trypanosoma brucei methionyl-tRNA synthetase were previously designed using a structure-guided approach. Compounds 1 and 2 were the most active compounds in the cyclic and linear linker series, respectively. To further improve cellular potency, SAR investigation of a binding fragment targeting the "enlarged methionine pocket" (EMP) was performed. The optimization led to the identification of a 6,8-dichloro-tetrahydroquinoline ring as a favorable fragment to bind the EMP. Replacement of 3,5-dichloro-benzyl group (the EMP binding fragment) of inhibitor 2 using this tetrahydroquinoline fragment resulted in compound 13, that exhibited an EC50 of 4nM.
+
-
 
+
-
Optimization of a binding fragment targeting the "enlarged methionine pocket" leads to potent Trypanosoma brucei methionyl-tRNA synthetase inhibitors.,Huang W, Zhang Z, Ranade RM, Gillespie JR, Barros-Alvarez X, Creason SA, Shibata S, Verlinde CLMJ, Hol WGJ, Buckner FS, Fan E Bioorg Med Chem Lett. 2017 Jun 15;27(12):2702-2707. doi:, 10.1016/j.bmcl.2017.04.048. Epub 2017 Apr 17. PMID:28465105<ref>PMID:28465105</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 5v49" style="background-color:#fffaf0;"></div>
+
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Methionine--tRNA ligase]]
+
[[Category: Trypanosoma brucei brucei TREU927]]
-
[[Category: Tryb2]]
+
[[Category: Barros-Alvarez X]]
-
[[Category: Barros-Alvarez, X]]
+
[[Category: Hol WGJ]]
-
[[Category: Hol, W G.J]]
+
-
[[Category: Inhibitor]]
+
-
[[Category: Ligase]]
+
-
[[Category: Ligase-ligase inhibitor complex]]
+
-
[[Category: Methionine]]
+
-
[[Category: Synthetase]]
+

Current revision

Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (Chem 1917)

PDB ID 5v49

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5v49"
Personal tools