6G1O

Structure of Pseudomonas aeruginosa Isocitrate Lyase, ICL

6G1O の概要

• エントリーDOI: 10.2210/pdb6g1o/pdb
• 分子名称: Isocitrate lyase, CALCIUM ION, GLYOXYLIC ACID, ... (4 entities in total)
• 機能のキーワード: isocitrate lyase, pseudomonas, tca cycle, lyase
• 由来する生物種: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54181.23

構造登録者

Crousilles, A.,Welch, M. (登録日: 2018-03-21, 公開日: 2018-08-01, 最終更新日: 2024-01-17)

主引用文献

Crousilles, A.,Dolan, S.K.,Brear, P.,Chirgadze, D.Y.,Welch, M.
Gluconeogenic precursor availability regulates flux through the glyoxylate shunt inPseudomonas aeruginosa.
J. Biol. Chem., 293:14260-14269, 2018

PubMed Abstract: The glyoxylate shunt bypasses the oxidative decarboxylation steps of the tricarboxylic acid (TCA) cycle, thereby conserving carbon skeletons for gluconeogenesis and biomass production. In , carbon flux is redirected through the first enzyme of the glyoxylate shunt, isocitrate lyase (ICL), following phosphorylation and inactivation of the TCA cycle enzyme, isocitrate dehydrogenase (ICD), by the kinase/phosphatase, AceK. In contrast, mycobacterial species lack AceK and employ a phosphorylation-insensitive isocitrate dehydrogenase (IDH), which is allosterically activated by the product of ICL activity, glyoxylate. However, expresses IDH, ICD, ICL, and AceK, raising the question of how these enzymes are regulated to ensure proper flux distribution between the competing pathways. Here, we present the structure, kinetics, and regulation of ICL, IDH, and ICD from We found that flux partitioning is coordinated through reciprocal regulation of these enzymes, linking distribution of carbon flux to the availability of the key gluconeogenic precursors, oxaloacetate and pyruvate. Specifically, a greater abundance of these metabolites activated IDH and inhibited ICL, leading to increased TCA cycle flux. Regulation was also exerted through AceK-dependent phosphorylation of ICD; high levels of acetyl-CoA (which would be expected to accumulate when oxaloacetate is limiting) stimulated the kinase activity of AceK, whereas high levels of oxaloacetate stimulated its phosphatase activity. In summary, the TCA cycle-glyoxylate shunt branch point in has a complex enzymology that is profoundly different from those in other species characterized to date. Presumably, this reflects its predilection for consuming fatty acids, especially during infection scenarios.

PubMed: 30030382
DOI: 10.1074/jbc.RA118.004514

実験手法

X-RAY DIFFRACTION (1.882 Å)