ArticleMolecular systems biology2019
Systematic mapping of protein-metabolite interactions in central metabolism of Escherichia coli.
Article in Molecular systems biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- Simultaneous determination of free and total metabolite concentrations in proteinaceous specimens by 1DCell reports methods · 2026Article
- Article
- MultiNMRFit: a software to fit 1D and pseudo-2D NMR spectra.Bioinformatics (Oxford, England) · 2025Article
- Mapping protein-metabolite interactions iniScience · 2025Article
- Systematic identification of allosteric effectors inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Regulation of gene expression through protein-metabolite interactions.npj metabolic health and disease · 2025Review
- HNCGAT: a method for predicting plant metabolite-protein interaction using heterogeneous neighbor contrastive graph attention network.Briefings in bioinformatics · 2024Article
- Back to the Future of Metabolism-Advances in the Discovery and Characterization of Unknown Biocatalytic Functions and Pathways.Life (Basel, Switzerland) · 2024Review
- MPI-VGAE: protein-metabolite enzymatic reaction link learning by variational graph autoencoders.Briefings in bioinformatics · 2023Article
- An automated workflow for multi-omics screening of microbial model organisms.NPJ systems biology and applications · 2023Article
- PrePCI: A structure- and chemical similarity-informed database of predicted protein compound interactions.Protein science : a publication of the Protein Society · 2023Article
- Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase.Science (New York, N.Y.) · 2023Article
- The Knowns and Unknowns in Protein-Metabolite Interactions.International journal of molecular sciences · 2023Review
- Protein-Metabolite Interactions Shape Cellular Metabolism and Physiology.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Prediction of metabolite-protein interactions based on integration of machine learning and constraint-based modeling.Bioinformatics advances · 2023Article
- Carbon-negative production of acetone and isopropanol by gas fermentation at industrial pilot scale.Nature biotechnology · 2022Article
- Advances and Trends in Omics Technology Development.Frontiers in medicine · 2022Review
- Studying Metabolism by NMR-Based Metabolomics.Frontiers in molecular biosciences · 2022Review
- Biclique extension as an effective approach to identify missing links in metabolic compound-protein interaction networks.Bioinformatics advances · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolite binding to proteins regulates nearly all cellular processes, but our knowledge of these interactions originates primarily from empirical in vitro studies. Here, we report the first systematic study of interactions between water-soluble proteins and polar metabolites in an entire biological subnetwork. To test the depth of our current knowledge, we chose to investigate the well-characterized Escherichia coli central metabolism. Using ligand-detected NMR, we assayed 29 enzymes towards binding events with 55 intracellular metabolites. Focusing on high-confidence interactions at a false-positive rate of 5%, we detected 98 interactions, among which purine nucleotides accounted for one-third, while 50% of all metabolites did not interact with any enzyme. In contrast, only five enzymes did not exhibit any metabolite binding and some interacted with up to 11 metabolites. About 40% of the interacting metabolites were predicted to be allosteric effectors based on low chemical similarity to their target's reactants. For five of the eight tested interactions, in vitro assays confirmed novel regulatory functions, including ATP and GTP inhibition of the first pentose phosphate pathway enzyme. With 76 new candidate regulatory interactions that have not been reported previously, we essentially doubled the number of known interactions, indicating that the presently available information about protein-metabolite interactions may only be the tip of the iceberg.
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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.