English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Structure-based electron-confurcation mechanism of the Ldh-EtfAB complex

Kayastha, K., Katsyv, A., Himmrich, C., Welsch, S., Schuller, J. M., Ermler, U., et al. (2022). Structure-based electron-confurcation mechanism of the Ldh-EtfAB complex. eLife, 11: e77095. doi:10.7554/eLife.77095.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Kayastha, Kanwal1, Author           
Katsyv, Alexander2, Author
Himmrich, Christina2, Author
Welsch, Sonja3, Author           
Schuller, Jan M.4, Author
Ermler, Ulrich1, Author           
Müller, Volker2, Author
Affiliations:
1Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max Planck Society, ou_2068290              
2Department of Molecular Microbiology & Bioenergetics, Institute of Molecular Biosciences, Goethe University, Frankfurt am Main, Germany, ou_persistent22              
3Central Electron Microscopy Facility, Max Planck Institute of Biophysics, Max Planck Society, ou_3249263              
4SYNMICRO Research Center and Department of Chemistry, Philipps University, Marburg, Germany, ou_persistent22              

Content

show
hide
Free keywords: biochemistry, bioenergetics, chemical biology, cryo-EM structure, electron bifurcation, electron-transferring flavoprotein, flavin, lactate dehydrogenase
 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)2 complex of Acetobacterium woodii 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.

Details

show
hide
Language(s): eng - English
 Dates: 2022-01-142022-05-222022-06-24
 Publication Status: Published online
 Pages: 19
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.7554/eLife.77095
BibTex Citekey: kayastha_structure-based_2022
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: eLife
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 11 Sequence Number: e77095 Start / End Page: - Identifier: ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X