6S2U
Structure of the catalytic domain of T. thermophilus Rel in complex with AMP and ppGpp
Summary for 6S2U
| Entry DOI | 10.2210/pdb6s2u/pdb |
| Descriptor | (P)ppGpp synthetase I, SpoT/RelA, MANGANESE (II) ION, ADENOSINE MONOPHOSPHATE, ... (7 entities in total) |
| Functional Keywords | ppgpp synthetase, ppgpp hydrolase, ppgpp, translation, stringent response, transferase |
| Biological source | Thermus thermophilus |
| Total number of polymer chains | 1 |
| Total formula weight | 41833.94 |
| Authors | Garcia-Pino, A. (deposition date: 2019-06-22, release date: 2020-07-08, Last modification date: 2024-01-24) |
| Primary citation | Tamman, H.,Van Nerom, K.,Takada, H.,Vandenberk, N.,Scholl, D.,Polikanov, Y.,Hofkens, J.,Talavera, A.,Hauryliuk, V.,Hendrix, J.,Garcia-Pino, A. A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes. Nat.Chem.Biol., 16:834-840, 2020 Cited by PubMed Abstract: Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3' pyrophosphate hydrolysis to degrade it. The regulation of the opposing activities of Rel enzymes is a complex allosteric mechanism that remains an active research topic despite decades of research. We show that a guanine-nucleotide-switch mechanism controls catalysis by Thermus thermophilus Rel (Rel). The binding of GDP/ATP opens the N-terminal catalytic domains (NTD) of Rel (Rel) by stretching apart the two catalytic domains. This activates the synthetase domain and allosterically blocks hydrolysis. Conversely, binding of ppGpp to the hydrolase domain closes the NTD, burying the synthetase active site and precluding the binding of synthesis precursors. This allosteric mechanism is an activity switch that safeguards against futile cycles of alarmone synthesis and degradation. PubMed: 32393900DOI: 10.1038/s41589-020-0520-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.95 Å) |
Structure validation
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