5U3C

CryoEM structure of the CTP synthase filament at 4.6 Angstrom resolution

5U3C の概要

• エントリーDOI: 10.2210/pdb5u3c/pdb
• 関連するPDBエントリー: 5U6R
• EMDBエントリー: 8504 8513
• 分子名称: CTP synthase, CYTIDINE-5'-TRIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: nucleotide metabolism, metabolic filament, protein fibril, ligase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 245429.35

構造登録者

Kollman, J.M.,Lynch, E.M. (登録日: 2016-12-01, 公開日: 2017-04-26, 最終更新日: 2024-11-20)

主引用文献

Lynch, E.M.,Hicks, D.R.,Shepherd, M.,Endrizzi, J.A.,Maker, A.,Hansen, J.M.,Barry, R.M.,Gitai, Z.,Baldwin, E.P.,Kollman, J.M.
Human CTP synthase filament structure reveals the active enzyme conformation.
Nat. Struct. Mol. Biol., 24:507-514, 2017

PubMed Abstract: The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that for human CTPS, polymerization increases catalytic activity. The cryo-EM structures of bacterial and human CTPS filaments differ considerably in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The structure of human CTPS filament, the first structure of the full-length human enzyme, reveals a novel active conformation. The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. The findings may provide a mechanism for increasing human CTPS activity in response to metabolic state and challenge the assumption that metabolic filaments are generally storage forms of inactive enzymes. Allosteric regulation of CTPS polymerization by ligands likely represents a fundamental mechanism underlying assembly of other metabolic filaments.

PubMed: 28459447
DOI: 10.1038/nsmb.3407

実験手法

ELECTRON MICROSCOPY (4.6 Å)