8YJO

Structure of E. coli glycyl radical enzyme PflD with bound malonate

8YJO の概要

• エントリーDOI: 10.2210/pdb8yjo/pdb
• 分子名称: Probable dehydratase PflD, MALONATE ION (3 entities in total)
• 機能のキーワード: glycyl radical enzyme, lyase
• 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: 175700.62

構造登録者

Xue, B.,Wei, Y.,Robinson, R.C.,Yew, W.S.,Zhang, Y. (登録日: 2024-03-02, 公開日: 2024-10-02, 最終更新日: 2024-10-09)

主引用文献

Ma, K.,Xue, B.,Chu, R.,Zheng, Y.,Sharma, S.,Jiang, L.,Hu, M.,Xie, Y.,Hu, Y.,Tao, T.,Zhou, Y.,Liu, D.,Li, Z.,Yang, Q.,Chen, Y.,Wu, S.,Tong, Y.,Robinson, R.C.,Yew, W.S.,Jin, X.,Liu, Y.,Zhao, H.,Ang, E.L.,Wei, Y.,Zhang, Y.
A Widespread Radical-Mediated Glycolysis Pathway.
J.Am.Chem.Soc., 146:26187-26197, 2024

PubMed Abstract: Glycyl radical enzymes (GREs) catalyze mechanistically diverse radical-mediated reactions, playing important roles in the metabolism of anaerobic bacteria. The model bacterium MG1655 contains two GREs of unknown function, YbiW and PflD, which are widespread among human intestinal bacteria. Here, we report that YbiW and PflD catalyze ring-opening C-O cleavage of 1,5-anhydroglucitol-6-phosphate (AG6P) and 1,5-anhydromannitol-6-phosphate (AM6P), respectively. The product of both enzymes, 1-deoxy-fructose-6-phosphate (DF6P), is then cleaved by the aldolases FsaA or FsaB to form glyceraldehyde-3-phosphate (G3P) and hydroxyacetone (HA), which are then reduced by the NADH-dependent dehydrogenase GldA to form 1,2-propanediol (1,2-PDO). Crystal structures of YbiW and PflD in complex with their substrates provided insights into the mechanism of radical-mediated C-O cleavage. This "anhydroglycolysis" pathway enables anaerobic growth of on 1,5-anhydroglucitol (AG) and 1,5-anhydromannitol (AM), and we probe the feasibility of harnessing this pathway for the production of 1,2-PDO, a highly demanded chiral chemical feedstock, from inexpensive starch. Discovery of the anhydroglycolysis pathway expands the known catalytic repertoire of GREs, clarifies the hitherto unknown physiological functions of the well-studied enzymes FsaA, FsaB, and GldA, and demonstrates how enzyme discovery efforts can cast light on prevalent yet overlooked metabolites in the microbiome.

PubMed: 39283600
DOI: 10.1021/jacs.4c07718

実験手法

X-RAY DIFFRACTION (1.8 Å)