6HL9

Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate

6HL9 の概要

• エントリーDOI: 10.2210/pdb6hl9/pdb
• 分子名称: Glutarate 2-hydroxylase, FE (II) ION, SUCCINIC ACID, ... (4 entities in total)
• 機能のキーワード: jelly roll, glutarate hydroxylase, alpha-ketoglutarate-dependent, hydrolase
• 由来する生物種: Escherichia coli (strain K12)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81641.48

構造登録者

Williams, R.M.,Mayans, O.,Hartig, J.S. (登録日: 2018-09-10, 公開日: 2019-02-20, 最終更新日: 2024-02-07)

主引用文献

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

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: 30498244
DOI: 10.1038/s41467-018-07563-6

実験手法

X-RAY DIFFRACTION (2.3 Å)