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Title: H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle

Abstract

Recent investigations into ferredoxin-dependent transhydrogenases, a class of enzymes responsible for electron transport, have highlighted the biological importance of flavin-based electron bifurcation (FBEB). FBEB generates biomolecules with very low reduction potential by coupling the oxidation of an electron donor with intermediate potential to the reduction of high and low potential molecules. Bifurcating systems can generate biomolecules with very low reduction potentials, such as reduced ferredoxin (Fd), from species such as NADPH. Metabolic systems that use bifurcation are more efficient and confer a competitive advantage for the organisms that harbor them. Structural models are now available for two NADH-dependent ferredoxin-NADP+ oxidoreductase (Nfn) complexes. These models, together with spectroscopic studies, have provided considerable insight into the catalytic process of FBEB. However, much about the mechanism and regulation of these multi-subunit proteins remains unclear. Using hydrogen/deuterium exchange mass spectrometry (HDX-MS) and statistical coupling analysis (SCA), we identified in this work specific pathways of communication within the model FBEB system, Nfn from Pyrococus furiosus, under conditions at each step of the catalytic cycle. HDX-MS revealed evidence for allosteric coupling across protein subunits upon nucleotide and ferredoxin binding. SCA uncovered a network of co-evolving residues that can provide connectivity across the complex. Together, the HDX-MSmore » and SCA data show that protein allostery occurs across the ensemble of iron-sulfur cofactors and ligand binding sites using specific pathways that connect domains allowing them to function as dynamically coordinated units.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [2];  [2];  [3];  [1];  [1]
+ Show Author Affiliations
  1. Montana State Univ., Bozeman, MT (United States)
  2. Univ. of Georgia, Athens, GA (United States)
  3. Washington State Univ., Pullman, WA (United States)
Publication Date:
Research Org.:
Energy Frontier Research Centers (EFRC) (United States). Center for Biological Electron Transfer and Catalysis (BETCy)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
OSTI Identifier:
1469904
Alternate Identifier(s):
OSTI ID: 1549363
Grant/Contract Number:  
SC0012518; P20GM103474
Resource Type:
Accepted Manuscript
Journal Name:
Biochimica et Biophysica Acta - General Subjects
Additional Journal Information:
Journal Volume: 1862; Journal Issue: 1; Related Information: BETCy partners with Montana State University (lead); Arizona State University; National Renewable Energy Laboratory; University of Georgia; University of Kentucky; University of Washington; Utah State University; Journal ID: ISSN 0304-4165
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; solar (fuels); biofuels (including algae and biomass); bio-inspired; hydrogen and fuel cells; HDX-MS; SCA; Electron bifurcation; Allostery; Ferredoxin-dependent transhydrogenase; Flavin-based electron bifurcation

Citation Formats

Berry, Luke, Poudel, Saroj, Tokmina-Lukaszewska, Monika, Colman, Daniel R., Nguyen, Diep M. N., Schut, Gerrit J., Adams, Michael W. W., Peters, John W., Boyd, Eric S., and Bothner, Brian. H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle. United States: N. p., 2017. Web. doi:10.1016/j.bbagen.2017.10.002.
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Berry, Luke, Poudel, Saroj, Tokmina-Lukaszewska, Monika, Colman, Daniel R., Nguyen, Diep M. N., Schut, Gerrit J., Adams, Michael W. W., Peters, John W., Boyd, Eric S., & Bothner, Brian. H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle. United States. https://doi.org/10.1016/j.bbagen.2017.10.002
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Berry, Luke, Poudel, Saroj, Tokmina-Lukaszewska, Monika, Colman, Daniel R., Nguyen, Diep M. N., Schut, Gerrit J., Adams, Michael W. W., Peters, John W., Boyd, Eric S., and Bothner, Brian. Fri . "H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle". United States. https://doi.org/10.1016/j.bbagen.2017.10.002. https://www.osti.gov/servlets/purl/1469904.
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@article{osti_1469904,
title = {H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle},
author = {Berry, Luke and Poudel, Saroj and Tokmina-Lukaszewska, Monika and Colman, Daniel R. and Nguyen, Diep M. N. and Schut, Gerrit J. and Adams, Michael W. W. and Peters, John W. and Boyd, Eric S. and Bothner, Brian},
abstractNote = {Recent investigations into ferredoxin-dependent transhydrogenases, a class of enzymes responsible for electron transport, have highlighted the biological importance of flavin-based electron bifurcation (FBEB). FBEB generates biomolecules with very low reduction potential by coupling the oxidation of an electron donor with intermediate potential to the reduction of high and low potential molecules. Bifurcating systems can generate biomolecules with very low reduction potentials, such as reduced ferredoxin (Fd), from species such as NADPH. Metabolic systems that use bifurcation are more efficient and confer a competitive advantage for the organisms that harbor them. Structural models are now available for two NADH-dependent ferredoxin-NADP+ oxidoreductase (Nfn) complexes. These models, together with spectroscopic studies, have provided considerable insight into the catalytic process of FBEB. However, much about the mechanism and regulation of these multi-subunit proteins remains unclear. Using hydrogen/deuterium exchange mass spectrometry (HDX-MS) and statistical coupling analysis (SCA), we identified in this work specific pathways of communication within the model FBEB system, Nfn from Pyrococus furiosus, under conditions at each step of the catalytic cycle. HDX-MS revealed evidence for allosteric coupling across protein subunits upon nucleotide and ferredoxin binding. SCA uncovered a network of co-evolving residues that can provide connectivity across the complex. Together, the HDX-MS and SCA data show that protein allostery occurs across the ensemble of iron-sulfur cofactors and ligand binding sites using specific pathways that connect domains allowing them to function as dynamically coordinated units.},
doi = {10.1016/j.bbagen.2017.10.002},
journal = {Biochimica et Biophysica Acta - General Subjects},
number = 1,
volume = 1862,
place = {United States},
year = {2017},
month = {10}
}
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https://doi.org/10.1016/j.bbagen.2017.10.002
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    Works referencing / citing this record:

    On the nature of organic and inorganic centers that bifurcate electrons, coupling exergonic and endergonic oxidation–reduction reactions
    journal, January 2018

    • Peters, John W.; Beratan, David N.; Schut, Gerrit J.
    • Chemical Communications, Vol. 54, Issue 33
    • DOI: 10.1039/c8cc01530a

    Origin and Evolution of Flavin-Based Electron Bifurcating Enzymes
    journal, August 2018

    Residue-Level Allostery Propagates through the Effective Coarse-Grained Hessian
    journal, April 2020

    • Lake, Peter T.; Davidson, Russell B.; Klem, Heidi
    • Journal of Chemical Theory and Computation, Vol. 16, Issue 5
    • DOI: 10.1021/acs.jctc.9b01149
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