7QH2

Cryo-EM structure of Ldh-EtfAB complex from Acetobacterium woodii

7QH2 の概要

• エントリーDOI: 10.2210/pdb7qh2/pdb
• EMDBエントリー: 13960
• 分子名称: Lactate dehydrogenase (NAD(+),ferredoxin) subunit LctC, Lactate dehydrogenase (NAD(+),ferredoxin) subunit LctB, Lactate dehydrogenase (NAD(+),ferredoxin) subunit LctD, ... (6 entities in total)
• 機能のキーワード: electron bifurcation, electron confirmation, lactate, lactate dehydrogenase complex, electron transferring flavoprotein, a. woodii, redox enzyme, flavoprotein
• 由来する生物種: Acetobacterium woodii; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 258180.83

構造登録者

Kayastha, K.,Ermler, U. (登録日: 2021-12-10, 公開日: 2022-06-29, 最終更新日: 2025-12-24)

主引用文献

Kayastha, K.,Katsyv, A.,Himmrich, C.,Welsch, S.,Schuller, J.M.,Ermler, U.,Muller, V.
Structure-based electron-confurcation mechanism of the Ldh-EtfAB complex.
Elife, 11:-, 2022

PubMed Abstract: Lactate oxidation with NAD as electron acceptor is a highly endergonic reaction. Some anaerobic bacteria overcome the energetic hurdle by flavin-based electron bifurcation/confurcation (FBEB/FBEC) using a lactate dehydrogenase (Ldh) in concert with the electron-transferring proteins EtfA and EtfB. The electron cryo-microscopically characterized (Ldh-EtfAB) complex of at 2.43 Å resolution consists of a mobile EtfAB shuttle domain located between the rigid central Ldh and the peripheral EtfAB base units. The FADs of Ldh and the EtfAB shuttle domain contact each other thereby forming the D (dehydrogenation-connected) state. The intermediary Glu37 and Glu139 may harmonize the redox potentials between the FADs and the pyruvate/lactate pair crucial for FBEC. By integrating Alphafold2 calculations a plausible novel B (bifurcation-connected) state was obtained allowing electron transfer between the EtfAB base and shuttle FADs. Kinetic analysis of enzyme variants suggests a correlation between NAD binding site and D-to-B-state transition implicating a 75° rotation of the EtfAB shuttle domain. The FBEC inactivity when truncating the ferredoxin domain of EtfA substantiates its role as redox relay. Lactate oxidation in Ldh is assisted by the catalytic base His423 and a metal center. On this basis, a comprehensive catalytic mechanism of the FBEC process was proposed.

PubMed: 35748623
DOI: 10.7554/eLife.77095

実験手法

ELECTRON MICROSCOPY (2.43 Å)