7D5C
IleRS in complex with a tRNA site inhibitor
Summary for 7D5C
| Entry DOI | 10.2210/pdb7d5c/pdb |
| Descriptor | Isoleucine--tRNA ligase, cytoplasmic, (2E,4S,5S,6E,8E)-10-[(2S,3R,6S,8R,9S)-3-butyl-9-methyl-2-[(1E,3E)-3-methyl-5-oxidanyl-5-oxidanylidene-penta-1,3-dienyl]-3-(4-oxidanyl-4-oxidanylidene-butanoyl)oxy-1,7-dioxaspiro[5.5]undecan-8-yl]-4,8-dimethyl-5-oxidanyl-deca-2,6,8-trienoic acid, [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] (2S,3S)-2-azanyl-3-methyl-pentanoate, ... (5 entities in total) |
| Functional Keywords | trna synthetase, ligase-inhibitor complex, ligase/inhibitor |
| Biological source | Saccharomyces cerevisiae S288c (Baker's yeast) |
| Total number of polymer chains | 1 |
| Total formula weight | 115414.30 |
| Authors | |
| Primary citation | Chen, B.,Luo, S.,Zhang, S.,Ju, Y.,Gu, Q.,Xu, J.,Yang, X.L.,Zhou, H. Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase. Nat Commun, 12:1616-1616, 2021 Cited by PubMed Abstract: 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 binding site of Saccharomyces cerevisiae IleRS (ScIleRS), by partially mimicking the binding of tRNA. RM-A binding is facilitated by the copurified intermediate product isoleucyl-adenylate (Ile-AMP). The binding assays confirm that RM-A competes with tRNA 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. PubMed: 33712620DOI: 10.1038/s41467-021-21902-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.895 Å) |
Structure validation
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