9J0H

The crystal structure of styrene monooxygenase StyA from Streptomyces vilmorinianum

Summary for 9J0H

• Entry DOI: 10.2210/pdb9j0h/pdb
• Descriptor: styrene monooxygenase/indole monooxygenase family protein (2 entities in total)
• Functional Keywords: styrene monooxygenase, stya, oxidoreductase
• Biological source: Streptomyces vilmorinianum
• Total number of polymer chains: 7
• Total formula weight: 334331.54

Authors

Wang, L.,Zhou, J. (deposition date: 2024-08-02, release date: 2025-03-19, Last modification date: 2025-05-14)

Primary citation

Li, Z.P.,Wang, L.,Liu, Y.,Pei, X.Q.,Fatmi, M.Q.,Shen, Z.,Zhao, J.,Lin, H.,Zhou, J.,Wu, Z.L.
Structural and Mechanistic Insight into the Enantioselectivity of (R)-Selective Styrene Monooxygenases: A Tug-of-War between Proximal and Distal Residues.
Angew.Chem.Int.Ed.Engl., 64:e202423117-e202423117, 2025

PubMed Abstract: Group E flavoprotein monooxygenases (GEMs) are well-known for catalyzing enantioselective epoxidation reactions. However, engineering their enantioselectivity remains a significant challenge, largely due to a limited understanding of the underlying mechanisms. Among these enzymes, (R)-selective styrene monooxygenases ((R)-SMOs) stand out due to their unusual enantio-switch behavior when catalyzing the reactions of p-substituted styrenes. This unique property provides an exceptional opportunity to investigate the enantiocontrol mechanisms within GEMs. In this study, we resolved the first crystal structure of an (R)-SMO, SeStyA, derived from Streptomyces. By integrating this structural information with molecular docking and molecular dynamics (MD) simulations, we identified four key residues critical to enantiodivergency: two distal residues (S178 and A219) and two proximal residues (A59 and A312). Strikingly, a "tug-of-war" mechanism was revealed through saturation mutagenesis, wherein the side-chain sizes of proximal and distal residues exerted opposing influences on enantioselectivity at the C=C bond. Leveraging this mechanistic insight, we successfully engineered SMOs with excellent (R)- or (S)-enantioselectivity.

PubMed: 39950369
DOI: 10.1002/anie.202423117

Experimental method

X-RAY DIFFRACTION (2.86 Å)