Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli
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...
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| Format: | Article |
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Springer Nature
2019-08-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20199008 |
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| author | Maren Diether Yaroslav Nikolaev Frédéric HT Allain Uwe Sauer |
| author_facet | Maren Diether Yaroslav Nikolaev Frédéric HT Allain Uwe Sauer |
| author_sort | Maren Diether |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4586648bbd6e4aae9d16bfd20a2de217 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2019-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-4586648bbd6e4aae9d16bfd20a2de2172025-08-20T04:02:50ZengSpringer NatureMolecular Systems Biology1744-42922019-08-0115811610.15252/msb.20199008Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coliMaren Diether0Yaroslav Nikolaev1Frédéric HT Allain2Uwe Sauer3Institute of Molecular Systems Biology, ETH ZurichInstitute of Molecular Biology and Biophysics, ETH ZurichInstitute of Molecular Biology and Biophysics, ETH ZurichInstitute of Molecular Systems Biology, ETH ZurichAbstract 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.https://doi.org/10.15252/msb.20199008allosterycentral metabolismnuclear magnetic resonanceprotein–metabolite interactionsregulation |
| spellingShingle | Maren Diether Yaroslav Nikolaev Frédéric HT Allain Uwe Sauer Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli Molecular Systems Biology allostery central metabolism nuclear magnetic resonance protein–metabolite interactions regulation |
| title | Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli |
| title_full | Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli |
| title_fullStr | Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli |
| title_full_unstemmed | Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli |
| title_short | Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli |
| title_sort | systematic mapping of protein metabolite interactions in central metabolism of escherichia coli |
| topic | allostery central metabolism nuclear magnetic resonance protein–metabolite interactions regulation |
| url | https://doi.org/10.15252/msb.20199008 |
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