7P4G

Rabbit Muscle L-lactate dehydrogenase in complex with citrate

7P4G の概要

• エントリーDOI: 10.2210/pdb7p4g/pdb
• 分子名称: L-lactate dehydrogenase A chain, CITRIC ACID (3 entities in total)
• 機能のキーワード: ldh, dehydrogenase, lactate, glycolysis, oxidoreductase
• 由来する生物種: Oryctolagus cuniculus (Rabbit)
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 588650.74

構造登録者

Iacovino, L.G.,Binda, C.,Hochkoeppler, A. (登録日: 2021-07-11, 公開日: 2022-05-18, 最終更新日: 2024-01-31)

主引用文献

Iacovino, L.G.,Rossi, M.,Di Stefano, G.,Rossi, V.,Binda, C.,Brigotti, M.,Tomaselli, F.,Pasti, A.P.,Dal Piaz, F.,Cerini, S.,Hochkoeppler, A.
Allosteric transitions of rabbit skeletal muscle lactate dehydrogenase induced by pH-dependent dissociation of the tetrameric enzyme.
Biochimie, 199:23-35, 2022

PubMed Abstract: Among the functions exerted by eukaryotic lactate dehydrogenases, it is of importance the generation of lactate in muscles subjected to fatigue or to limited oxygen availability, with both these conditions triggering a decrease of cellular pH. However, the mutual dependence between lactate dehydrogenase (LDH) catalytic action and lactic acidosis is far from being fully understood. Here we show that the tetrameric LDH from rabbit skeletal muscle undergoes allosteric transitions as a function of pH, i.e. the enzyme obeys Michaelis-Menten kinetics at neutral or slightly alkaline pH values, and features sigmoidal kinetics at pH 6.5 or lower. Remarkably, we also report that a significant dissociation of tetrameric rabbit LDH occurs under acidic conditions, with pyruvate/NAD or citrate counteracting this effect. Moreover, citrate strongly activates rabbit LDH, inducing the enzyme to feature Michaelis-Menten kinetics. Further, using primary rabbit skeletal muscle cells we tested the generation of lactate as a function of pH, and we detected a parallel decrease of cytosolic pH and secretion of lactate. Overall, our observations indicate that lactic acidosis is antagonized by LDH dissociation, the occurrence of which is regulated by citrate and by allosteric transitions of the enzyme induced by pyruvate.

PubMed: 35398441
DOI: 10.1016/j.biochi.2022.03.008

実験手法

X-RAY DIFFRACTION (2.6 Å)