Structural highlights
4p3o is a 2 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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Ligands: | , , |
Related: | 4p3n, 4p3p |
Gene: | thrS, b1719, JW1709 ("Bacillus coli" Migula 1895) |
Activity: | Threonine--tRNA ligase, with EC number 6.1.1.3 |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[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]
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fang P, Yu X, Jeong SJ, Mirando A, Chen K, Chen X, Kim S, Francklyn CS, Guo M. Structural basis for full-spectrum inhibition of translational functions on a tRNA synthetase. Nat Commun. 2015 Mar 31;6:6402. doi: 10.1038/ncomms7402. PMID:25824639 doi:http://dx.doi.org/10.1038/ncomms7402