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Title: A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme

Abstract

Multielectron redox reactions often require multicofactor metalloenzymes to facilitate coupled electron and proton movement, but it is challenging to design artificial enzymes to catalyze these important reactions, owing to their structural and functional complexity. We report a designed heteronuclear heme-[4Fe-4S] cofactor in cytochromecperoxidase as a structural and functional model of the enzyme sulfite reductase. The initial model exhibits spectroscopic and ligand-binding properties of the native enzyme, and sulfite reduction activity was improved—through rational tuning of the secondary sphere interactions around the [4Fe-4S] and the substrate-binding sites—to be close to that of the native enzyme. By offering insight into the requirements for a demanding six-electron, seven-proton reaction that has so far eluded synthetic catalysts, this study provides strategies for designing highly functional multicofactor artificial enzymes.

Authors:
ORCiD logo; ORCiD logo; ORCiD logo; ; ORCiD logo
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1490222
Report Number(s):
PNNL-SA-138512
Journal ID: ISSN 0036-8075
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Science
Additional Journal Information:
Journal Volume: 361; Journal Issue: 6407; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
English

Citation Formats

Mirts, Evan N., Petrik, Igor D., Hosseinzadeh, Parisa, Nilges, Mark J., and Lu, Yi. A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme. United States: N. p., 2018. Web. doi:10.1126/science.aat8474.
Mirts, Evan N., Petrik, Igor D., Hosseinzadeh, Parisa, Nilges, Mark J., & Lu, Yi. A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme. United States. doi:10.1126/science.aat8474.
Mirts, Evan N., Petrik, Igor D., Hosseinzadeh, Parisa, Nilges, Mark J., and Lu, Yi. Thu . "A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme". United States. doi:10.1126/science.aat8474.
@article{osti_1490222,
title = {A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme},
author = {Mirts, Evan N. and Petrik, Igor D. and Hosseinzadeh, Parisa and Nilges, Mark J. and Lu, Yi},
abstractNote = {Multielectron redox reactions often require multicofactor metalloenzymes to facilitate coupled electron and proton movement, but it is challenging to design artificial enzymes to catalyze these important reactions, owing to their structural and functional complexity. We report a designed heteronuclear heme-[4Fe-4S] cofactor in cytochromecperoxidase as a structural and functional model of the enzyme sulfite reductase. The initial model exhibits spectroscopic and ligand-binding properties of the native enzyme, and sulfite reduction activity was improved—through rational tuning of the secondary sphere interactions around the [4Fe-4S] and the substrate-binding sites—to be close to that of the native enzyme. By offering insight into the requirements for a demanding six-electron, seven-proton reaction that has so far eluded synthetic catalysts, this study provides strategies for designing highly functional multicofactor artificial enzymes.},
doi = {10.1126/science.aat8474},
journal = {Science},
issn = {0036-8075},
number = 6407,
volume = 361,
place = {United States},
year = {2018},
month = {9}
}

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