7Z98

Crystal structure of F191M variant Variovorax paradoxus indole monooxygenase (VpIndA1) in complex with methyl phenyl sulfide

Summary for 7Z98

• Entry DOI: 10.2210/pdb7z98/pdb
• Descriptor: Putative dehydrogenase/oxygenase subunit (Flavoprotein), FLAVIN-ADENINE DINUCLEOTIDE, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: fad-dependent monooxygenase, styrene monooxygenase, stya1, imo, oxidoreductase
• Biological source: Variovorax paradoxus EPS
• Total number of polymer chains: 1
• Total formula weight: 48342.48

Authors

Kratky, J.,Weisse, R.,Strater, N. (deposition date: 2022-03-20, release date: 2023-02-22, Last modification date: 2024-02-07)

Primary citation

Kratky, J.,Eggerichs, D.,Heine, T.,Hofmann, S.,Sowa, P.,Weisse, R.H.,Tischler, D.,Strater, N.
Structural and Mechanistic Studies on Substrate and Stereoselectivity of the Indole Monooxygenase VpIndA1: New Avenues for Biocatalytic Epoxidations and Sulfoxidations.
Angew.Chem.Int.Ed.Engl., 62:e202300657-e202300657, 2023

PubMed Abstract: Flavoprotein monooxygenases are a versatile group of enzymes for biocatalytic transformations. Among these, group E monooxygenases (GEMs) catalyze enantioselective epoxidation and sulfoxidation reactions. Here, we describe the crystal structure of an indole monooxygenase from the bacterium Variovorax paradoxus EPS, a GEM designated as VpIndA1. Complex structures with substrates reveal productive binding modes that, in conjunction with force-field calculations and rapid mixing kinetics, reveal the structural basis of substrate and stereoselectivity. Structure-based redesign of the substrate cavity yielded variants with new substrate selectivity (for sulfoxidation of benzyl phenyl sulfide) or with greatly enhanced stereoselectivity (from 35.1 % to 99.8 % ee for production of (1S,2R)-indene oxide). This first determination of the substrate binding mode of GEMs combined with structure-function relationships opens the door for structure-based design of these powerful biocatalysts.

PubMed: 36762980
DOI: 10.1002/anie.202300657

Experimental method

X-RAY DIFFRACTION (1.73 Å)