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

Mirts, Evan N.; Petrik, Igor D.; Hosseinzadeh, Parisa; Nilges, Mark J.; Lu, Yi

doi:10.1126/science.aat8474

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

Journal Article · Thu Sep 13 00:00:00 EDT 2018 · Science

DOI:https://doi.org/10.1126/science.aat8474· OSTI ID:1490222

;

; Nilges, Mark J.;

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.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1490222

Report Number(s):: PNNL-SA-138512

Journal Information:: Science, Vol. 361, Issue 6407; ISSN 0036-8075

Publisher:: AAAS

Country of Publication:: United States

Language:: English

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