Issue 16, 2024

Electronic isomerism in a heterometallic nickel–iron–sulfur cluster models substrate binding and cyanide inhibition of carbon monoxide dehydrogenase

Abstract

The nickel–iron carbon monoxide dehydrogenase (CODH) enzyme uses a heterometallic nickel–iron–sulfur ([NiFe4S4]) cluster to catalyze the reversible interconversion of carbon dioxide (CO2) and carbon monoxide (CO). These reactions are essential for maintaining the global carbon cycle and offer a route towards sustainable greenhouse gas conversion but have not been successfully replicated in synthetic models, in part due to a poor understanding of the natural system. Though the general protein architecture of CODH is known, the electronic structure of the active site is not well-understood, and the mechanism of catalysis remains unresolved. To better understand the CODH enzyme, we have developed a protein-based model containing a heterometallic [NiFe3S4] cluster in the Pyrococcus furiosus (Pf) ferredoxin (Fd). This model binds small molecules such as carbon monoxide and cyanide, analogous to CODH. Multiple redox- and ligand-bound states of [NiFe3S4] Fd (NiFd) have been investigated using a suite of spectroscopic techniques, including resonance Raman, Ni and Fe K-edge X-ray absorption spectroscopy, and electron paramagnetic resonance, to resolve charge and spin delocalization across the cluster, site-specific electron density, and ligand activation. The facile movement of charge through the cluster highlights the fluidity of electron density within iron–sulfur clusters and suggests an electronic basis by which CN inhibits the native system while the CO-bound state continues to elude isolation in CODH. The detailed characterization of isolable states that are accessible in our CODH model system provides valuable insight into unresolved enzymatic intermediates and offers design principles towards developing functional mimics of CODH.

Graphical abstract: Electronic isomerism in a heterometallic nickel–iron–sulfur cluster models substrate binding and cyanide inhibition of carbon monoxide dehydrogenase

Supplementary files

Article information

Article type
Edge Article
Submitted
02 jan 2024
Accepted
04 mar 2024
First published
27 mar 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2024,15, 5916-5928

Electronic isomerism in a heterometallic nickel–iron–sulfur cluster models substrate binding and cyanide inhibition of carbon monoxide dehydrogenase

L. C. Lewis, J. A. Sanabria-Gracia, Y. Lee, A. J. Jenkins and H. S. Shafaat, Chem. Sci., 2024, 15, 5916 DOI: 10.1039/D4SC00023D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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