8XHX

The complex structure of PaBcmG and its natural substrate

This is a non-PDB format compatible entry.

Summary for 8XHX

• Entry DOI: 10.2210/pdb8xhx/pdb
• Descriptor: Fe/2OG dependent dioxygenase, 2-OXOGLUTARIC ACID, (3~{S},6~{S})-3-(2-methyl-2-oxidanyl-propyl)-6-[(2~{S})-4-oxidanylbutan-2-yl]piperazine-2,5-dione, ... (6 entities in total)
• Functional Keywords: c-h activation, fe/2og dependent dioxygenase, bicyclomycin, oxidoreductase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 35546.56

Authors

Wu, L.,Tang, G.L.,Zhou, J.H. (deposition date: 2023-12-18, release date: 2025-05-28)

Primary citation

Wu, L.,He, J.B.,Wei, W.,Pan, H.X.,Wang, X.,Yang, S.,Liang, Y.,Tang, G.L.,Zhou, J.
Three distinct strategies lead to programmable aliphatic C-H oxidation in bicyclomycin biosynthesis.
Nat Commun, 16:4651-4651, 2025

PubMed Abstract: The C-H bond functionalization has been widely used in chemical synthesis over the past decade. However, regio- and stereoselectivity still remain a significant challenge, especially for inert aliphatic C-H bonds. Here we report the mechanism of three Fe(II)/α-ketoglutarate-dependent dioxygenases in bicyclomycin synthesis, which depicts the natural tactic to sequentially hydroxylate specific C-H bonds of similar substrates (cyclodipeptides). Molecular basis by crystallographic studies, computational simulations, and site-directed mutagenesis reveals the exquisite arrangement of three enzymes using mutually orthogonal strategies to realize three different regio-selectivities. Moreover, this programmable selective hydroxylation can be extended to other cyclodipeptides. This evidence not only provides a naturally occurring showcase corresponding to the widely used methods in chemical catalysis but also expands the toolbox of biocatalysts to address the regioselective functionalization of C-H bonds.

PubMed: 40389404
DOI: 10.1038/s41467-025-58997-8

Experimental method

X-RAY DIFFRACTION (1.61000421314 Å)