5LLB

Structure of Polyphosphate Kinase 2 from Francisella tularensis with AMPPCH2PPP and polyphosphate

5LLB の概要

• エントリーDOI: 10.2210/pdb5llb/pdb
• 関連するPDBエントリー: 4YEG
• 分子名称: Polyphosphate kinase 2, CHLORIDE ION, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: complex with non-hydrolysable atp analogue. polyphosphate metabolism. nucleotide metabolism, transferase
• 由来する生物種: Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132013.76

構造登録者

Roach, P.L.,Parnell, A.E. (登録日: 2016-07-27, 公開日: 2017-10-11, 最終更新日: 2024-01-10)

主引用文献

Parnell, A.E.,Mordhorst, S.,Kemper, F.,Giurrandino, M.,Prince, J.P.,Schwarzer, N.J.,Hofer, A.,Wohlwend, D.,Jessen, H.J.,Gerhardt, S.,Einsle, O.,Oyston, P.C.F.,Andexer, J.N.,Roach, P.L.
Substrate recognition and mechanism revealed by ligand-bound polyphosphate kinase 2 structures.
Proc. Natl. Acad. Sci. U.S.A., 115:3350-3355, 2018

PubMed Abstract: Inorganic polyphosphate is a ubiquitous, linear biopolymer built of up to thousands of phosphate residues that are linked by energy-rich phosphoanhydride bonds. Polyphosphate kinases of the family 2 (PPK2) use polyphosphate to catalyze the reversible phosphorylation of nucleotide phosphates and are highly relevant as targets for new pharmaceutical compounds and as biocatalysts for cofactor regeneration. PPK2s can be classified based on their preference for nucleoside mono- or diphosphates or both. The detailed mechanism of PPK2s and the molecular basis for their substrate preference is unclear, which is mainly due to the lack of high-resolution structures with substrates or substrate analogs. Here, we report the structural analysis and comparison of a class I PPK2 (ADP-phosphorylating) and a class III PPK2 (AMP- and ADP-phosphorylating), both complexed with polyphosphate and/or nucleotide substrates. Together with complementary biochemical analyses, these define the molecular basis of nucleotide specificity and are consistent with a Mg catalyzed in-line phosphoryl transfer mechanism. This mechanistic insight will guide the development of PPK2 inhibitors as potential antibacterials or genetically modified PPK2s that phosphorylate alternative substrates.

PubMed: 29531036
DOI: 10.1073/pnas.1710741115

実験手法

X-RAY DIFFRACTION (1.92 Å)