6UDP

Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Filament assembly interface reconstruction.

6UDP の概要

• エントリーDOI: 10.2210/pdb6udp/pdb
• 関連するPDBエントリー: 6U8E 6U8N 6U8R 6U8S 6U9O 6UA2 6UA4 6UA5 6UAJ 6UC2 6UDO
• EMDBエントリー: 20687 20688 20690 20691 20701 20704 20705 20706 20707 20709 20716 20718 20720 20722 20723 20725 20741 20742
• 分子名称: Inosine-5'-monophosphate dehydrogenase 2, INOSINIC ACID (2 entities in total)
• 機能のキーワード: metabolism, filament, allostery, adenine, guanine, biosynthetic protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 454629.65

構造登録者

Johnson, M.C.,Kollman, J.M. (登録日: 2019-09-19, 公開日: 2020-03-25, 最終更新日: 2025-06-04)

主引用文献

Johnson, M.C.,Kollman, J.M.
Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation.
Elife, 9:-, 2020

PubMed Abstract: Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. IMPDH reversibly polymerizes in cells and tissues in response to changes in metabolic demand. Self-assembly of metabolic enzymes is increasingly recognized as a general mechanism for regulating activity, typically by stabilizing specific conformations of an enzyme, but the regulatory role of IMPDH filaments has remained unclear. Here, we report a series of human IMPDH2 cryo-EM structures in both active and inactive conformations. The structures define the mechanism of filament assembly, and reveal how filament-dependent allosteric regulation of IMPDH2 makes the enzyme less sensitive to feedback inhibition, explaining why assembly occurs under physiological conditions that require expansion of guanine nucleotide pools. Tuning sensitivity to an allosteric inhibitor distinguishes IMPDH from other metabolic filaments, and highlights the diversity of regulatory outcomes that can emerge from self-assembly.

PubMed: 31999252
DOI: 10.7554/eLife.53243

実験手法

ELECTRON MICROSCOPY (2.95 Å)