7d5c | pdb_00007d5c

IleRS in complex with a tRNA site inhibitor

spinqualitylabelsall models 7d5c, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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. Ligands: EDO, GV6, GVU 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminoacyl tRNA synthetase 3D structures

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