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4p3p

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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SYT_ECOLI SYT_ECOLI]] ThrS is also a translational repressor protein, it controls the translation of its own gene by binding to its mRNA.[HAMAP-Rule:MF_00184]
[[http://www.uniprot.org/uniprot/SYT_ECOLI SYT_ECOLI]] ThrS is also a translational repressor protein, it controls the translation of its own gene by binding to its mRNA.[HAMAP-Rule:MF_00184]
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== Publication Abstract from PubMed ==
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The polyketide natural product borrelidin displays antibacterial, antifungal, antimalarial, anticancer, insecticidal and herbicidal activities through the selective inhibition of threonyl-tRNA synthetase (ThrRS). How borrelidin simultaneously attenuates bacterial growth and suppresses a variety of infections in plants and animals is not known. Here we show, using X-ray crystal structures and functional analyses, that a single molecule of borrelidin simultaneously occupies four distinct subsites within the catalytic domain of bacterial and human ThrRSs. These include the three substrate-binding sites for amino acid, ATP and tRNA associated with aminoacylation, and a fourth 'orthogonal' subsite created as a consequence of binding. Thus, borrelidin competes with all three aminoacylation substrates, providing a potent and redundant mechanism to inhibit ThrRS during protein synthesis. These results highlight a surprising natural design to achieve the quadrivalent inhibition of translation through a highly conserved family of enzymes.
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Structural basis for full-spectrum inhibition of translational functions on a tRNA synthetase.,Fang P, Yu X, Jeong SJ, Mirando A, Chen K, Chen X, Kim S, Francklyn CS, Guo M Nat Commun. 2015 Mar 31;6:6402. doi: 10.1038/ncomms7402. PMID:25824639<ref>PMID:25824639</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
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<references/>
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</StructureSection>
</StructureSection>

Revision as of 06:58, 15 April 2015

Structural Basis for Full-Spectrum Inhibition of Threonyl-tRNA Synthetase by Borrelidin 3

4p3p, resolution 2.10Å

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