Publication Abstract from PubMed
The two-component flavoenzyme styrene monooxygenase (SMO) is an efficient alternative to several chemical epoxidation catalysts on a preparative scale. A first homology model of the catalytic domain (StyA) of SMO was constructed (Protein Data Bank ID 2HD8) based on the structure of para-hydroxybenzoate hydroxylase. The StyA protein structure was optimized by restrained molecular dynamics to reproduce specific pre-S binding orientations of styrene. Effects of all 10 point mutations examined were explained by the distance of the site to the styrene and FAD binding sites. Thirteen of 20 ligands could be accommodated in a catalytically active binding orientation, and predicted affinities correlated well with experimental turnover and inhibition. The binding cavity is almost completely hydrophobic except for a hydrogen-bonded network formed by three water molecules, the backbone of residues 300-302, and the flavin ribityl, similar to P293, and three crystal waters in para-hydroxybenzoate hydroxylase suggest that P302, T47, and the waters in StyA are a vital component of the catalytic mechanism. The current optimized and validated StyA model provides a good starting point for elucidation of the structural basis of StyA ligand binding and catalysis. Novel insights in the binding of ligands to SMO/StyA, provided by the current protein model, will aid the rational design of mutants with specific, altered enantioselective properties.
Enantioselective substrate binding in a monooxygenase protein model by molecular dynamics and docking.,Feenstra KA, Hofstetter K, Bosch R, Schmid A, Commandeur JN, Vermeulen NP Biophys J. 2006 Nov 1;91(9):3206-16. Epub 2006 Aug 11. PMID:16905618[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
