7XN3

E.coli phosphoribosylpyrophosphate (PRPP) synthetase type B filament bound with Pi

7XN3 の概要

• エントリーDOI: 10.2210/pdb7xn3/pdb
• EMDBエントリー: 33309
• 分子名称: Ribose-phosphate pyrophosphokinase, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: allosteric enzyme, kinase, transferase, nucleotide biosynthesis, atp-binding, magnesium, manganese, metal-binding, nucleotide-binding, biosynthetic protein
• 由来する生物種: Escherichia coli str. K-12 substr. MG1655
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 211644.19

構造登録者

Hu, H.H.,Lu, G.M.,Chang, C.C.,Liu, J.L. (登録日: 2022-04-27, 公開日: 2022-06-29, 最終更新日: 2024-07-03)

主引用文献

Hu, H.H.,Lu, G.M.,Chang, C.C.,Li, Y.,Zhong, J.,Guo, C.J.,Zhou, X.,Yin, B.,Zhang, T.,Liu, J.L.
Filamentation modulates allosteric regulation of PRPS.
Elife, 11:-, 2022

PubMed Abstract: Phosphoribosyl pyrophosphate (PRPP) is a key intermediate in the biosynthesis of purine and pyrimidine nucleotides, histidine, tryptophan, and cofactors NAD and NADP. Abnormal regulation of PRPP synthase (PRPS) is associated with human disorders, including Arts syndrome, retinal dystrophy, and gouty arthritis. Recent studies have demonstrated that PRPS can form filamentous cytoophidia in eukaryotes. Here, we show that PRPS forms cytoophidia in prokaryotes both in vitro and in vivo. Moreover, we solve two distinct filament structures of PRPS at near-atomic resolution using Cryo-EM. The formation of the two types of filaments is controlled by the binding of different ligands. One filament type is resistant to allosteric inhibition. The structural comparison reveals conformational changes of a regulatory flexible loop, which may regulate the binding of the allosteric inhibitor and the substrate ATP. A noncanonical allosteric AMP/ADP binding site is identified to stabilize the conformation of the regulatory flexible loop. Our findings not only explore a new mechanism of PRPS regulation with structural basis, but also propose an additional layer of cell metabolism through PRPS filamentation.

PubMed: 35736577
DOI: 10.7554/eLife.79552

実験手法

ELECTRON MICROSCOPY (2.9 Å)