6CZF

The structure of E. coli PurF in complex with ppGpp-Mg

6CZF の概要

• エントリーDOI: 10.2210/pdb6czf/pdb
• 分子名称: Amidophosphoribosyltransferase, MAGNESIUM ION, GUANOSINE-5',3'-TETRAPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: purf, ppgpp, transferase
• 由来する生物種: Escherichia coli (strain K12)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 224150.77

構造登録者

Wang, B.,Grant, R.A.,Laub, M.T. (登録日: 2018-04-09, 公開日: 2018-10-10, 最終更新日: 2023-10-04)

主引用文献

Wang, B.,Dai, P.,Ding, D.,Del Rosario, A.,Grant, R.A.,Pentelute, B.L.,Laub, M.T.
Affinity-based capture and identification of protein effectors of the growth regulator ppGpp.
Nat. Chem. Biol., 15:141-150, 2019

PubMed Abstract: The nucleotide ppGpp is a highly conserved regulatory molecule in bacteria that helps tune growth rate to nutrient availability. Despite decades of study, how ppGpp regulates growth remains poorly understood. Here, we developed and validated a capture-compound mass spectrometry approach that identified >50 putative ppGpp targets in Escherichia coli. These targets control many key cellular processes and include 13 enzymes required for nucleotide synthesis. We demonstrated that ppGpp inhibits the de novo synthesis of all purine nucleotides by directly targeting the enzyme PurF. By solving a structure of PurF bound to ppGpp, we designed a mutation that ablates ppGpp-based regulation, leading to dysregulation of purine-nucleotide synthesis following ppGpp accumulation. Collectively, our results provide new insights into ppGpp-based growth control and a nearly comprehensive set of targets for future exploration. The capture compounds developed should also enable the rapid identification of ppGpp targets in any species, including pathogens.

PubMed: 30559427
DOI: 10.1038/s41589-018-0183-4

実験手法

X-RAY DIFFRACTION (1.949 Å)