ArticleJournal of the American Chemical Society2012
Are free radicals involved in IspH catalysis? An EPR and crystallographic investigation.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 48 citations in OpenAlex.
- Resonance Raman Spectroscopic Study of the Unusual [4Fe-4S]Chembiochem : a European journal of chemical biology · 2025Article
- Iron-Sulfur Cluster Enzymes of the Methylerythritol Phosphate Pathway: IspG and IspH.Biochemistry · 2025Review
- The Reductive Dehydroxylation Catalyzed by IspH, a Source of Inspiration for the Development of Novel Anti-Infectives.Molecules (Basel, Switzerland) · 2022Review
- Microbial (Frontiers in bioengineering and biotechnology · 2022Review
- Spectroscopic and Computational Investigations of Ligand Binding to IspH: Discovery of Non-diphosphate Inhibitors.Chembiochem : a European journal of chemical biology · 2017Article
- The Enzymology of Organic Transformations: A Survey of Name Reactions in Biological Systems.Angewandte Chemie (International ed. in English) · 2017Review
- Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme.Journal of the American Chemical Society · 2016Article
- Two unexpected promiscuous activities of the iron-sulfur protein IspH in production of isoprene and isoamylene.Microbial cell factories · 2016Article
- Mechanistic insights into the reductive dehydroxylation pathway for the biosynthesis of isoprenoids promoted by the IspH enzyme.Chemical science · 2015Article
- Broken-Symmetry DFT Computations for the Reaction Pathway of IspH, an Iron-Sulfur Enzyme in Pathogenic Bacteria.Inorganic chemistry · 2015Article
- Advanced paramagnetic resonance spectroscopies of iron-sulfur proteins: Electron nuclear double resonance (ENDOR) and electron spin echo envelope modulation (ESEEM).Biochimica et biophysica acta · 2015Review
- The amino-terminal conserved domain of 4-hydroxy-3-methylbut-2-enyl diphosphate reductase is critical for its function in oxygen-evolving photosynthetic organisms.Plant signaling & behavior · 2015Article
- Use of Broken-Symmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition.Journal of chemical theory and computation · 2014Article
- Functional evidence for the critical amino-terminal conserved domain and key amino acids of Arabidopsis 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE.Plant physiology · 2014Article
- Insights into the binding of pyridines to the iron-sulfur enzyme IspH.Journal of the American Chemical Society · 2014Article
- Bioorganometallic chemistry with IspG and IspH: structure, function, and inhibition of the [Fe(4)S(4)] proteins involved in isoprenoid biosynthesis.Angewandte Chemie (International ed. in English) · 2014Review
- Inhibition of the 4Fe-4S Proteins IspG and IspH: an EPR, ENDOR and HYSCORE Investigation.Chemical science · 2014Article
- Isoprenoid biosynthesis: ferraoxetane or allyl anion mechanism for IspH catalysis?Angewandte Chemie (International ed. in English) · 2013Article
- Structures of fluoro, amino, and thiol inhibitors bound to the [Fe4S4] protein IspH.Angewandte Chemie (International ed. in English) · 2013Article
- Inhibition of IspH, a [4Fe-4S]2+ enzyme involved in the biosynthesis of isoprenoids via the methylerythritol phosphate pathway.Journal of the American Chemical Society · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The [4Fe-4S] protein IspH in the methylerythritol phosphate isoprenoid biosynthesis pathway is an important anti-infective drug target, but its mechanism of action is still the subject of debate. Here, by using electron paramagnetic resonance (EPR) spectroscopy and (2)H, (17)O, and (57)Fe isotopic labeling, we have characterized and assigned two key reaction intermediates in IspH catalysis. The results are consistent with the bioorganometallic mechanism proposed earlier, and the mechanism is proposed to have similarities to that of ferredoxin, thioredoxin reductase, in that one electron is transferred to the [4Fe-4S](2+) cluster, which then performs a formal two-electron reduction of its substrate, generating an oxidized high potential iron-sulfur protein (HiPIP)-like intermediate. The two paramagnetic reaction intermediates observed correspond to the two intermediates proposed in the bioorganometallic mechanism: the early π-complex in which the substrate's 3-CH(2)OH group has rotated away from the reduced iron-sulfur cluster, and the next, η(3)-allyl complex formed after dehydroxylation. No free radical intermediates are observed, and the two paramagnetic intermediates observed do not fit in a Birch reduction-like or ferraoxetane mechanism. Additionally, we show by using EPR spectroscopy and X-ray crystallography that two substrate analogues (4 and 5) follow the same reaction mechanism.
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Registered trials
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