5k0s: Difference between revisions
New page: ==Crystal structure of methionyl-tRNA synthetase MetRS from Brucella melitensis in complex with inhibitor Chem 1312== <StructureSection load='5k0s' size='340' side='right' caption='[[5k0s... |
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==Crystal structure of methionyl-tRNA synthetase MetRS from Brucella melitensis in complex with inhibitor Chem 1312== | ==Crystal structure of methionyl-tRNA synthetase MetRS from Brucella melitensis in complex with inhibitor Chem 1312== | ||
<StructureSection load='5k0s' size='340' side='right' caption='[[5k0s]], [[Resolution|resolution]] 2.45Å' scene=''> | <StructureSection load='5k0s' size='340' side='right'caption='[[5k0s]], [[Resolution|resolution]] 2.45Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5k0s]] is a 3 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4lne 4lne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K0S OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5k0s]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Brucella_suis_1330 Brucella suis 1330]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4lne 4lne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K0S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K0S FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0OU:2-({3-[(3,5-DICHLOROBENZYL)AMINO]PROPYL}AMINO)QUINOLIN-4(1H)-ONE'>0OU</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=5k0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k0s OCA], [https://pdbe.org/5k0s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k0s RCSB], [https://www.ebi.ac.uk/pdbsum/5k0s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k0s ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/SYM_BRUSU SYM_BRUSU] Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with molecular, structural and phenotypic methods to learn if BmMetRS is a promising target for brucellosis drug development. Recombinant BmMetRS was expressed, purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP #DD-156 and screened by a thermal melt assay against a focused library of one hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood stage form of Trypanosoma brucei. Three compounds showed appreciable shift of denaturation temperature and were selected for further studies on inhibition of the recombinant enzyme activity and cell viability against wild type B. melitensis strain 16M. BmMetRS protein complexed with these three inhibitors resolved into three-dimensional crystal structures and was analyzed. All three selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS enzymatic functions in an aminoacylation assay at varying concentrations. Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS is a promising target for brucellosis drug development. However, further studies are needed to optimize lead compound potency, efficacy and safety as well as determine the pharmacokinetics, optimal dosage, and duration for effective treatment. | |||
Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis.,Ojo KK, Ranade RM, Zhang Z, Dranow DM, Myers JB, Choi R, Nakazawa Hewitt S, Edwards TE, Davies DR, Lorimer D, Boyle SM, Barrett LK, Buckner FS, Fan E, Van Voorhis WC PLoS One. 2016 Aug 8;11(8):e0160350. doi: 10.1371/journal.pone.0160350., eCollection 2016. PMID:27500735<ref>PMID:27500735</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5k0s" 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: Brucella suis 1330]] | ||
[[Category: | [[Category: Large Structures]] | ||