6S2U

Structure of the catalytic domain of T. thermophilus Rel in complex with AMP and ppGpp

6S2U の概要

• エントリーDOI: 10.2210/pdb6s2u/pdb
• 分子名称: (P)ppGpp synthetase I, SpoT/RelA, MANGANESE (II) ION, ADENOSINE MONOPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: ppgpp synthetase, ppgpp hydrolase, ppgpp, translation, stringent response, transferase
• 由来する生物種: Thermus thermophilus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41833.94

構造登録者

Garcia-Pino, A. (登録日: 2019-06-22, 公開日: 2020-07-08, 最終更新日: 2024-01-24)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.95 Å)