4QBT
Crystal structure of tyrosine bound human tyrosyl tRNA synthetase
Summary for 4QBT
| Entry DOI | 10.2210/pdb4qbt/pdb |
| Related | 4Q93 |
| Descriptor | Tyrosine--tRNA ligase, cytoplasmic, PHOSPHATE ION, POTASSIUM ION, ... (7 entities in total) |
| Functional Keywords | tyrosine, aminoacyl trna synthetase, rossman fold, aminoacid activation, trna, ester bond, ligase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 42958.11 |
| Authors | Mathew, S.,Schimmel, P. (deposition date: 2014-05-08, release date: 2014-12-17, Last modification date: 2023-09-20) |
| Primary citation | Sajish, M.,Schimmel, P. A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. Nature, 519:370-373, 2014 Cited by PubMed Abstract: Resveratrol is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects by initiating a stress response that induces survival genes. Because human tyrosyl transfer-RNA (tRNA) synthetase (TyrRS) translocates to the nucleus under stress conditions, we considered the possibility that the tyrosine-like phenolic ring of resveratrol might fit into the active site pocket to effect a nuclear role. Here we present a 2.1 Å co-crystal structure of resveratrol bound to the active site of TyrRS. Resveratrol nullifies the catalytic activity and redirects TyrRS to a nuclear function, stimulating NAD(+)-dependent auto-poly-ADP-ribosylation of poly(ADP-ribose) polymerase 1 (PARP1). Downstream activation of key stress signalling pathways are causally connected to TyrRS-PARP1-NAD(+) collaboration. This collaboration is also demonstrated in the mouse, and is specifically blocked in vivo by a resveratrol-displacing tyrosyl adenylate analogue. In contrast to functionally diverse tRNA synthetase catalytic nulls created by alternative splicing events that ablate active sites, here a non-spliced TyrRS catalytic null reveals a new PARP1- and NAD(+)-dependent dimension to the physiological mechanism of resveratrol. PubMed: 25533949DOI: 10.1038/nature14028 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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