ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structure, function and inhibition of the two- and three-domain 4Fe-4S IspG proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Iron-Sulfur Cluster Enzymes of the Methylerythritol Phosphate Pathway: IspG and IspH.Biochemistry · 2025Review
- The chromosome-scale genomes of two Tinospora species reveal differential regulation of the MEP pathway in terpenoid biosynthesis.BMC biology · 2025Article
- The methylerythritol phosphate pathway as an oxidative stress sense and response system.Nature communications · 2024Review
- The Multifaceted MEP Pathway: Towards New Therapeutic Perspectives.Molecules (Basel, Switzerland) · 2023Review
- Evolutionary flexibility and rigidity in the bacterial methylerythritol phosphate (MEP) pathway.Frontiers in microbiology · 2023Article
- Insights into the ObservedACS omega · 2021Article
- Positioning Bacillus subtilis as terpenoid cell factory.Journal of applied microbiology · 2021Review
- The eukaryotic MEP-pathway genes are evolutionarily conserved and originated from Chlaymidia and cyanobacteria.BMC genomics · 2021Article
- Uncovering the functional residues ofProceedings of the National Academy of Sciences of the United States of America · 2020Article
- SEED CAROTENOID DEFICIENT Functions in Isoprenoid Biosynthesis via the Plastid MEP Pathway.Plant physiology · 2019Article
- The plastidial retrograde signal methyl erythritol cyclopyrophosphate is a regulator of salicylic acid and jasmonic acid crosstalk.Journal of experimental botany · 2016Article
- Metabolic engineering of Bacillus subtilis for terpenoid production.Applied microbiology and biotechnology · 2015Review
- Atomic-Resolution Structures of Discrete Stages on the Reaction Coordinate of the [Fe4S4] Enzyme IspG (GcpE).Journal of molecular biology · 2015Article
- 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
- Mechanistic aspects of carotenoid biosynthesis.Chemical reviews · 2014Review
- Are free radicals involved in IspH catalysis? An EPR and crystallographic investigation.Journal of the American Chemical Society · 2012Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
Abstract
IspG is a 4Fe4S protein involved in isoprenoid biosynthesis. Most bacterial IspGs contain two domains: a TIM barrel (A) and a 4Fe4S domain (B), but in plants and malaria parasites, there is a large insert domain (A*) whose structure and function are unknown. We show that bacterial IspGs function in solution as (AB)(2) dimers and that mutations in either both A or both B domains block activity. Chimeras harboring an A-mutation in one chain and a B-mutation in the other have 50% of the activity seen in wild-type protein, because there is still one catalytically active AB domain. However, a plant IspG functions as an AA*B monomer. We propose, using computational modeling and electron microscopy, that the A* insert domain has a TIM barrel structure that interacts with the A domain. This structural arrangement enables the A and B domains to interact in a "cup and ball" manner during catalysis, just as in the bacterial systems. EPR/HYSCORE spectra of reaction intermediate, product, and inhibitor ligands bound to both two and three domain proteins are identical, indicating the same local electronic structure, and computational docking indicates these ligands bridge both A and B domains. Overall, the results are of broad general interest because they indicate the insert domain in three-domain IspGs is a second TIM barrel that plays a structural role and that the pattern of inhibition of both two and three domain proteins are the same, results that can be expected to be of use in drug design.
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