6S2V

Structure of the N-terminal catalytic region of T. thermophilus Rel

Summary for 6S2V

• Entry DOI: 10.2210/pdb6s2v/pdb
• Descriptor: (P)ppGpp synthetase I, SpoT/RelA, MANGANESE (II) ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: ppgpp hydrolase, ppgpp synthetase, ppgpp, stringent response, translation, transferase
• Biological source: Thermus thermophilus
• Total number of polymer chains: 3
• Total formula weight: 122826.38

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

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: 32393900
DOI: 10.1038/s41589-020-0520-2

Experimental method

X-RAY DIFFRACTION (2.96 Å)