6GFL

Crystal structure of the Escherichia coli nucleosidase PpnN (apo form)

6GFL の概要

• エントリーDOI: 10.2210/pdb6gfl/pdb
• 関連するPDBエントリー: 6GFM
• 分子名称: Pyrimidine/purine nucleotide 5'-monophosphate nucleosidase (2 entities in total)
• 機能のキーワード: ygdh, ppnn, allosteric enzyme, nucleotide metabolism, stringent response, antibiotic tolerance, persistence, fluoroquinolone, hydrolase
• 由来する生物種: Escherichia coli K-12
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 106488.34

構造登録者

Zhang, Y.,Baerentsen, R.L.,Gerdes, K.,Brodersen, D.E. (登録日: 2018-05-01, 公開日: 2019-04-24, 最終更新日: 2024-10-09)

主引用文献

Zhang, Y.E.,Baerentsen, R.L.,Fuhrer, T.,Sauer, U.,Gerdes, K.,Brodersen, D.E.
(p)ppGpp Regulates a Bacterial Nucleosidase by an Allosteric Two-Domain Switch.
Mol.Cell, 74:1239-, 2019

PubMed Abstract: The stringent response alarmones pppGpp and ppGpp are essential for rapid adaption of bacterial physiology to changes in the environment. In Escherichia coli, the nucleosidase PpnN (YgdH) regulates purine homeostasis by cleaving nucleoside monophosphates and specifically binds (p)ppGpp. Here, we show that (p)ppGpp stimulates the catalytic activity of PpnN both in vitro and in vivo causing accumulation of several types of nucleobases during stress. The structure of PpnN reveals a tetramer with allosteric (p)ppGpp binding sites located between subunits. pppGpp binding triggers a large conformational change that shifts the two terminal domains to expose the active site, providing a structural rationale for the stimulatory effect. We find that PpnN increases fitness and adjusts cellular tolerance to antibiotics and propose a model in which nucleotide levels can rapidly be adjusted during stress by simultaneous inhibition of biosynthesis and stimulation of degradation, thus achieving a balanced physiological response to constantly changing environments.

PubMed: 31023582
DOI: 10.1016/j.molcel.2019.03.035

実験手法

X-RAY DIFFRACTION (2.48 Å)