View source for 4py2


==Crystal structure of methionyl-tRNA synthetase MetRS from Brucella melitensis in complex with inhibitor 1-{3-[(3,5-DICHLOROBENZYL)AMINO]PROPYL}-3-THIOPHEN-3-YLUREA==
<StructureSection load='4py2' size='340' side='right'caption='[[4py2]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4py2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Brucella_abortus_2308 Brucella abortus 2308]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PY2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=43E:1-{3-[(3,5-DICHLOROBENZYL)AMINO]PROPYL}-3-THIOPHEN-3-YLUREA'>43E</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4py2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4py2 OCA], [https://pdbe.org/4py2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4py2 RCSB], [https://www.ebi.ac.uk/pdbsum/4py2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4py2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q2YQ76_BRUA2 Q2YQ76_BRUA2] Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation (By similarity).[HAMAP-Rule:MF_01228][SAAS:SAAS023457_004_015657]
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4py2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Brucella abortus 2308]]
[[Category: Large Structures]]
[[Category: Structural genomic]]