ArticleProceedings of the National Academy of Sciences of the United States of America2013
Direct observation of structurally encoded metal discrimination and ether bond formation in a heterodinuclear metalloprotein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Bimetallic Chemistry by Design: Approaches to the Development of Multifunctional Ligands.Coordination chemistry reviews · 2026Article
- Unsymmetric bimetallic centres in metalloproteins and synthetic models.Nature reviews. Chemistry · 2026Review
- Electronic and Structural Heterogeneity in the Diiron Center of Sulerythrin: Insights From Hybrid QM/MM Calculations.Chemphyschem : a European journal of chemical physics and physical chemistry · 2026Article
- Selective isotope labeling probes the chemical capacity and reaction mechanism of a heterobimetallic Mn/Fe protein.Journal of inorganic biochemistry · 2025Article
- Structural Elucidation of the Reduced Mn(III)/Fe(III) Intermediate of the Radical-Initiating Metallocofactor inBiochemistry · 2025Article
- OJournal of the American Chemical Society · 2025Article
- Assembly of a Heterobimetallic Fe/Mn Cofactor in theBiochemistry · 2024Article
- Accessing a synthetic FeChemical science · 2024Article
- A novel alkane monooxygenase evolved from a broken piece of ribonucleotide reductase in Geobacillus kaustophilus HTA426 isolated from Mariana Trench.Extremophiles : life under extreme conditions · 2024Article
- Bioinformatic Discovery of a Cambialistic Monooxygenase.Journal of the American Chemical Society · 2024Article
- Enzymatic Hydroxylation of Aliphatic C-H Bonds by a Mn/Fe Cofactor.Journal of the American Chemical Society · 2023Article
- Steric Effects on the Chelation of MnChemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Enzymatic Hydroxylation of Aliphatic C-H Bonds by a Mn/Fe Cofactor.bioRxiv : the preprint server for biology · 2023Article
- Why is manganese so valuable to bacterial pathogens?Frontiers in cellular and infection microbiology · 2023Review
- Pulsed Multifrequency Electron Paramagnetic Resonance Spectroscopy Reveals Key Branch Points for One- vs Two-Electron Reactivity in Mn/Fe Proteins.Journal of the American Chemical Society · 2022Article
- Comparative structural analysis provides new insights into the function of R2-like ligand-binding oxidase.FEBS letters · 2022Article
- Ferritin-Like Proteins: A Conserved Core for a Myriad of Enzyme Complexes.Sub-cellular biochemistry · 2022Article
- Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules.The Journal of biological chemistry · 2021Review
- The Bacillus anthracis class Ib ribonucleotide reductase subunit NrdF intrinsically selects manganese over iron.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
- Key Structural Motifs Balance Metal Binding and Oxidative Reactivity in a Heterobimetallic Mn/Fe Protein.Journal of the American Chemical Society · 2020Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although metallocofactors are ubiquitous in enzyme catalysis, how metal binding specificity arises remains poorly understood, especially in the case of metals with similar primary ligand preferences such as manganese and iron. The biochemical selection of manganese over iron presents a particularly intricate problem because manganese is generally present in cells at a lower concentration than iron, while also having a lower predicted complex stability according to the Irving-Williams series (Mn(II) < Fe(II) < Ni(II) < Co(II) < Cu(II) > Zn(II)). Here we show that a heterodinuclear Mn/Fe cofactor with the same primary protein ligands in both metal sites self-assembles from Mn(II) and Fe(II) in vitro, thus diverging from the Irving-Williams series without requiring auxiliary factors such as metallochaperones. Crystallographic, spectroscopic, and computational data demonstrate that one of the two metal sites preferentially binds Fe(II) over Mn(II) as expected, whereas the other site is nonspecific, binding equal amounts of both metals in the absence of oxygen. Oxygen exposure results in further accumulation of the Mn/Fe cofactor, indicating that cofactor assembly is at least a two-step process governed by both the intrinsic metal specificity of the protein scaffold and additional effects exerted during oxygen binding or activation. We further show that the mixed-metal cofactor catalyzes a two-electron oxidation of the protein scaffold, yielding a tyrosine-valine ether cross-link. Theoretical modeling of the reaction by density functional theory suggests a multistep mechanism including a valyl radical intermediate.
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