9KDP

Crystal structure of monooxygenase PenE

Summary for 9KDP

• Entry DOI: 10.2210/pdb9kdp/pdb
• Descriptor: Anthrone monooxygenase (2 entities in total)
• Functional Keywords: monooxygenase, oxidoreductase
• Biological source: Saccharothrix espanaensis
• Total number of polymer chains: 4
• Total formula weight: 110692.06

Authors

Chi, C.B.,Ma, M. (deposition date: 2024-11-03, release date: 2025-07-09)

Primary citation

Shen, S.,Chi, C.,Fan, K.,Zhang, Q.,Xu, Y.,Gao, J.,Hu, H.,Wang, L.,Yang, D.,Ma, M.,Pan, G.
Functional Conservation and Divergence of AlpJ-Family Oxygenases Catalyzing C-C Bond Cleavage in Atypical Angucycline Biosynthesis.
Acs Chem.Biol., 2025

PubMed Abstract: AlpJ-family oxygenases catalyze distinctive oxidative B-ring cleavage and rearrangement reactions during the biosynthesis of atypical angucycline natural products, which are characterized by unique chemical structures and diverse biological activities. While the individual functions of a few AlpJ-family enzymes have been reported, there is a lack of systematic exploration and functional comparison within this enzyme family, hindering a comprehensive understanding of the AlpJ-family oxygenases. In this study, we have systematically explored and analyzed AlpJ-family oxygenases, identifying 49 representative homologues, which can be classified into two distinct evolutionary groups. We revealed that enzymes from different groups exhibit clear functional differentiation, catalyzing the same angucycline substrate dehydrorabelomycin into distinct products, whereas enzymes within the same group display more similar catalytic functions with varying degrees of functional overlap. This underscores the intriguing functional conservation and divergence of the AlpJ-family oxygenases. In addition, we report the first crystal structure of a Group I enzyme, PenE. Structural analysis and site-directed mutagenesis identified key structural features and residues within AlpJ-family oxygenases, which harbor hydrophobic substrate-binding pockets at both the N- and C-termini, both of which are essential for function. Our findings provide valuable insights into the evolution, catalytic mechanisms, and functional divergence of this unique family of oxygenases. Further investigation of these newly identified AlpJ homologues and their associated biosynthetic gene clusters will facilitate the discovery of enzymes with unique catalytic mechanisms and bioactive atypical angucyclines with novel structures.

PubMed: 40500926
DOI: 10.1021/acschembio.5c00040

Experimental method

X-RAY DIFFRACTION (2.592 Å)