ArticleJournal of the American Chemical Society2013
Spectroscopic studies of the mononuclear non-heme Fe(II) enzyme FIH: second-sphere contributions to reactivity.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Origins of Catalysis in Non-Heme Fe(II)/2-Oxoglutarate-Dependent Histone Lysine Demethylase KDM4A with Differently Methylated Histone H3 Peptides.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Article
- Gas Tunnel Engineering of Prolyl Hydroxylase Reprograms Hypoxia Signaling in Cells.Angewandte Chemie (International ed. in English) · 2024Article
- Gas tunnel engineering of prolyl hydroxylase reprograms hypoxia signaling in cells.bioRxiv : the preprint server for biology · 2024Article
- Structural, Spectroscopic, and Computational Insights from Canavanine-Bound and Two Catalytically Compromised Variants of the Ethylene-Forming Enzyme.Biochemistry · 2024Article
- From random to rational: improving enzyme design through electric fields, second coordination sphere interactions, and conformational dynamics.Chemical science · 2023Review
- Article
- β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin.Communications chemistry · 2022Article
- How Human TET2 Enzyme Catalyzes the Oxidation of Unnatural Cytosine Modifications in Double-Stranded DNA.ACS catalysis · 2022Article
- Electrostatic Perturbations in the Substrate-Binding Pocket of Taurine/α-Ketoglutarate Dioxygenase Determine its Selectivity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Heteroleptic Ligation by an endo-Functionalized Cage.Angewandte Chemie (International ed. in English) · 2021Article
- Epoxidation Catalyzed by the Nonheme Iron(II)- and 2-Oxoglutarate-Dependent Oxygenase, AsqJ: Mechanistic Elucidation of Oxygen Atom Transfer by a Ferryl Intermediate.Journal of the American Chemical Society · 2020Article
- Evaluation of a concerted vs. sequential oxygen activation mechanism in α-ketoglutarate-dependent nonheme ferrous enzymes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Protein Flexibility of the α-Ketoglutarate-Dependent Oxygenase Factor-Inhibiting HIF-1: Implications for Substrate Binding, Catalysis, and Regulation.Biochemistry · 2019Article
- Structures, Spectroscopic Properties, and Dioxygen Reactivity of 5- and 6-Coordinate Nonheme Iron(II) Complexes: A Combined Enzyme/Model Study of Thiol Dioxygenases.Journal of the American Chemical Society · 2018Article
- Chloride Supports OInorganic chemistry · 2018Article
- OJournal of the American Chemical Society · 2018Article
- Investigations on the role of a solvent tunnel in the α-ketoglutarate dependent oxygenase factor inhibiting HIF (FIH).Journal of inorganic biochemistry · 2018Article
- Magnetic circular dichroism studies of iron(ii) binding to human calprotectin.Chemical science · 2017Article
- The facial triad in the α-ketoglutarate dependent oxygenase FIH: A role for sterics in linking substrate binding to OJournal of inorganic biochemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Factor inhibiting hypoxia-inducible factor (FIH) is an α-ketoglutarate (αKG)-dependent enzyme which catalyzes hydroxylation of residue Asn803 in the C-terminal transactivation domain (CAD) of hypoxia-inducible factor 1α (HIF-1α) and plays an important role in cellular oxygen sensing and hypoxic response. Circular dichroism (CD), magnetic circular dichroism (MCD), and variable-temperature, variable-field (VTVH) MCD spectroscopies are used to determine the geometric and electronic structures of FIH in its (Fe(II)), (Fe(II)/αKG), and (Fe(II)/αKG/CAD) forms. (Fe(II))FIH and (Fe(II)/αKG)FIH are found to be six-coordinate (6C), whereas (Fe(II)/αKG/CAD)FIH is found to be a 5C/6C mixture. Thus, FIH follows the general mechanistic strategy of non-heme Fe(II) enzymes. Modeling shows that, when Arg238 of FIH is removed, the facial triad carboxylate binds to Fe(II) in a bidentate mode with concomitant lengthening of the Fe(II)/αKG carbonyl bond, which would inhibit the O2 reaction. Correlations over α-keto acid-dependent enzymes and with the extradiol dioxygenases show that members of these families (where both the electron source and O2 bind to Fe(II)) have a second-sphere residue H-bonding to the terminal oxygen of the carboxylate, which stays monodentate. Alternatively, structures of the pterin-dependent and Rieske dioxygenases, which do not have substrate binding to Fe(II), lack H-bonds to the carboxylate and thus allow its bidentate coordination which would direct O2 reactivity. Finally, vis-UV MCD spectra show an unusually high-energy Fe(II) → αKG π* metal-to-ligand charge transfer transition in (Fe(II)/αKG)FIH which is red-shifted upon CAD binding. This red shift indicates formation of H-bonds to the αKG that lower the energy of its carbonyl LUMO, activating it for nucleophilic attack by the Fe-O2 intermediate formed along the reaction coordinate.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.