Structural highlights
7d5c is a 1 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Gene: | ILS1, YBL076C, YBL0734 (Baker's yeast) |
| Activity: | Isoleucine--tRNA ligase, with EC number 6.1.1.5 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
The polyketide natural product reveromycin A (RM-A) exhibits antifungal, anticancer, anti-bone metastasis, anti-periodontitis and anti-osteoporosis activities by selectively inhibiting eukaryotic cytoplasmic isoleucyl-tRNA synthetase (IleRS). Herein, a co-crystal structure suggests that the RM-A molecule occupies the substrate tRNA(Ile) binding site of Saccharomyces cerevisiae IleRS (ScIleRS), by partially mimicking the binding of tRNA(Ile). RM-A binding is facilitated by the copurified intermediate product isoleucyl-adenylate (Ile-AMP). The binding assays confirm that RM-A competes with tRNA(Ile) while binding synergistically with L-isoleucine or intermediate analogue Ile-AMS to the aminoacylation pocket of ScIleRS. This study highlights that the vast tRNA binding site of the Rossmann-fold catalytic domain of class I aminoacyl-tRNA synthetases could be targeted by a small molecule. This finding will inform future rational drug design.
Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase.,Chen B, Luo S, Zhang S, Ju Y, Gu Q, Xu J, Yang XL, Zhou H Nat Commun. 2021 Mar 12;12(1):1616. doi: 10.1038/s41467-021-21902-0. PMID:33712620[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen B, Luo S, Zhang S, Ju Y, Gu Q, Xu J, Yang XL, Zhou H. Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase. Nat Commun. 2021 Mar 12;12(1):1616. doi: 10.1038/s41467-021-21902-0. PMID:33712620 doi:http://dx.doi.org/10.1038/s41467-021-21902-0
