6HL9
Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate
Summary for 6HL9
| Entry DOI | 10.2210/pdb6hl9/pdb |
| Descriptor | Glutarate 2-hydroxylase, FE (II) ION, SUCCINIC ACID, ... (4 entities in total) |
| Functional Keywords | jelly roll, glutarate hydroxylase, alpha-ketoglutarate-dependent, hydrolase |
| Biological source | Escherichia coli (strain K12) |
| Total number of polymer chains | 2 |
| Total formula weight | 81641.48 |
| Authors | Williams, R.M.,Mayans, O.,Hartig, J.S. (deposition date: 2018-09-10, release date: 2019-02-20, Last modification date: 2024-02-07) |
| Primary citation | Knorr, S.,Sinn, M.,Galetskiy, D.,Williams, R.M.,Wang, C.,Muller, N.,Mayans, O.,Schleheck, D.,Hartig, J.S. Widespread bacterial lysine degradation proceeding via glutarate and L-2-hydroxyglutarate. Nat Commun, 9:5071-5071, 2018 Cited by PubMed Abstract: Lysine degradation has remained elusive in many organisms including Escherichia coli. Here we report catabolism of lysine to succinate in E. coli involving glutarate and L-2-hydroxyglutarate as intermediates. We show that CsiD acts as an α-ketoglutarate-dependent dioxygenase catalysing hydroxylation of glutarate to L-2-hydroxyglutarate. CsiD is found widespread in bacteria. We present crystal structures of CsiD in complex with glutarate, succinate, and the inhibitor N-oxalyl-glycine, demonstrating strong discrimination between the structurally related ligands. We show that L-2-hydroxyglutarate is converted to α-ketoglutarate by LhgO acting as a membrane-bound, ubiquinone-linked dehydrogenase. Lysine enters the pathway via 5-aminovalerate by the promiscuous enzymes GabT and GabD. We demonstrate that repression of the pathway by CsiR is relieved upon glutarate binding. In conclusion, lysine degradation provides an important link in central metabolism. Our results imply the gut microbiome as a potential source of glutarate and L-2-hydroxyglutarate associated with human diseases such as cancer and organic acidurias. PubMed: 30498244DOI: 10.1038/s41467-018-07563-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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