6ECH

Pyruvate Kinase Isoform L-type with phosphorylated Ser12 (pS12) in complex with FBP

6ECH の概要

• エントリーDOI: 10.2210/pdb6ech/pdb
• 関連するPDBエントリー: 6ECK
• 分子名称: Pyruvate kinase PKLR, CHLORIDE ION, 1,6-di-O-phosphono-beta-D-fructofuranose, ... (11 entities in total)
• 機能のキーワード: pkl, pyruvate kinase, glycolysis, transferase
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 245832.23

構造登録者

Padyana, A.,Tong, S. (登録日: 2018-08-07, 公開日: 2019-12-04, 最終更新日: 2024-10-09)

主引用文献

Gassaway, B.M.,Cardone, R.L.,Padyana, A.K.,Petersen, M.C.,Judd, E.T.,Hayes, S.,Tong, S.,Barber, K.W.,Apostolidi, M.,Abulizi, A.,Sheetz, J.B.,Aerni, H.R.,Gross, S.,Kung, C.,Samuel, V.T.,Shulman, G.I.,Kibbey, R.G.,Rinehart, J.
Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production.
Cell Rep, 29:3394-3404.e9, 2019

PubMed Abstract: Pyruvate kinase is an important enzyme in glycolysis and a key metabolic control point. We recently observed a pyruvate kinase liver isoform (PKL) phosphorylation site at S113 that correlates with insulin resistance in rats on a 3 day high-fat diet (HFD) and suggests additional control points for PKL activity. However, in contrast to the classical model of PKL regulation, neither authentically phosphorylated PKL at S12 nor S113 alone is sufficient to alter enzyme kinetics or structure. Instead, we show that cyclin-dependent kinases (CDKs) are activated by the HFD and responsible for PKL phosphorylation at position S113 in addition to other targets. These CDKs control PKL nuclear retention, alter cytosolic PKL activity, and ultimately influence glucose production. These results change our view of PKL regulation and highlight a previously unrecognized pathway of hepatic CDK activity and metabolic control points that may be important in insulin resistance and type 2 diabetes.

PubMed: 31825824
DOI: 10.1016/j.celrep.2019.11.009

実験手法

X-RAY DIFFRACTION (2.19 Å)