98%
921
2 minutes
20
Oxoiron(IV) complexes are key intermediates in the catalytic reactions of some non-heme diiron enzymes. These enzymes, across various subfamilies, activate dioxygen to generate high-valent diiron-oxo species, which, in turn, drive the activation of substrates and mediate a variety of challenging oxidative transformations. In this review, we summarize the structures, formation mechanisms, and functions of high-valent diiron-oxo intermediates in eight representative diiron enzymes (sMMO, RNR, ToMO, MIOX, PhnZ, SCD1, AlkB, and SznF) spanning five subfamilies. We also categorize and analyze the structural and mechanistic differences among these enzymes.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/cbic.202400788 | DOI Listing |
Biochemistry
August 2025
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Ribonucleotide reductases (RNRs) generate 2'-deoxynucleotides for DNA biosynthesis, a reaction essential to all life. Class I RNRs have two subunits, α and β. α binds and reduces the substrate, whereas β oxidizes one of the cysteines in α to a C3'-H-bond-cleaving thiyl radical to begin the reaction.
View Article and Find Full Text PDFJ Am Chem Soc
August 2025
Department of Chemistry, University of California, Davis, California 95616, United States.
[FeFe] hydrogenases are highly efficient metalloenzymes that catalyze hydrogen conversion via a sophisticated active site cofactor known as the H-cluster. Biosynthesis of its [2Fe] subcluster, which contains CO, CN, and azadithiolate ligands, requires the action of several dedicated enzymes, including the radical -adenosyl-l-methionine (rSAM) enzyme HydE. HydE has been proposed to convert a mononuclear [Fe(II)(cysteinate)(CO)(CN)] precursor into a dimeric [Fe(SH)(CO)(CN)] complex, yet direct characterization of this product species has remained elusive.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Department of Chemistry, National Tsing Hua University, Hsinchu 300-044, Taiwan.
Pathogenic endures bursts of host-derived reactive nitrogen species, yet the molecular defenses that enable this resilience have remained unclear. We now show that the previously enigmatic di-iron enzyme ScdA functions as a nitrite reductase, converting nitrite to nitric oxide (NO), and we elucidate the structural elements that support this activity. Using an integrative toolkit─X-ray crystallography, solution NMR, AlphaFold modeling, and pulsed EPR/DEER─we solved the full-length homodimeric structure of ScdA and identified a robust di-iron center that forms stable iron-nitrosyl intermediates.
View Article and Find Full Text PDFJ Am Chem Soc
August 2025
Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.
Nonheme diiron enzymes activate dioxygen (O) to affect various biochemical outcomes. HrmI, a member of the recently discovered and functionally versatile heme oxygenase-like dimetal oxidase/oxygenase (HDO) superfamily, catalyzes the N-oxygenation of L-Lysine to yield 6-nitronorleucine for the biosynthesis of the antibiotic hormaomycin. Unlike other characterized HDO N-oxygenases that have an additional carboxylate ligand thought to be key for regulating dioxygen activation and ensuing N-oxygenation, the predicted primary coordination sphere of HrmI resembles those of HDOs that instead perform C-C fragmentation of substrates.
View Article and Find Full Text PDFInorg Chem
September 2025
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, India.
Diheme enzymes display redox cooperativity possibly via a tryptophan moiety placed in between two heme centers, thereby behaving as a single diheme unit rather than as two independent heme centers. Herein, we present an unprecedented, rationally designed dicobalt porphyrin dimer catalyzed hetero-Diels-Alder [4 + 2] reaction of unactivated aldehydes/imines with simple dienes under mild reaction conditions with extremely low catalyst loading. The high catalytic efficiency of the dimeric catalyst over the monomer and heterobimetallic Cu-Co catalyst highlights the importance of underlying cooperativity between two porphyrin units during catalysis.
View Article and Find Full Text PDF