1W4X

Phenylacetone Monooxygenase, a Baeyer-Villiger Monooxygenase

Summary for 1W4X

• Entry DOI: 10.2210/pdb1w4x/pdb
• Descriptor: PHENYLACETONE MONOOXYGENASE, FLAVIN-ADENINE DINUCLEOTIDE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: baeyer-villiger, monooxygenase, fad, oxygenase
• Biological source: THERMOBIFIDA FUSCA
• Total number of polymer chains: 1
• Total formula weight: 62073.06

Authors

Malito, E.,Alfieri, A.,Mattevi, A. (deposition date: 2004-08-03, release date: 2004-09-02, Last modification date: 2024-05-08)

Primary citation

Malito, E.,Alfieri, A.,Fraaije, M.W.,Mattevi, A.
Crystal Structure of a Baeyer-Villiger Monooxygenase
Proc.Natl.Acad.Sci.USA, 101:13157-, 2004

PubMed Abstract: Flavin-containing Baeyer-Villiger monooxygenases employ NADPH and molecular oxygen to catalyze the insertion of an oxygen atom into a carbon-carbon bond of a carbonylic substrate. These enzymes can potentially be exploited in a variety of biocatalytic applications given the wide use of Baeyer-Villiger reactions in synthetic organic chemistry. The catalytic activity of these enzymes involves the formation of two crucial intermediates: a flavin peroxide generated by the reaction of the reduced flavin with molecular oxygen and the "Criegee" intermediate resulting from the attack of the flavin peroxide onto the substrate that is being oxygenated. The crystal structure of phenylacetone monooxygenase, a Baeyer-Villiger monooxygenase from the thermophilic bacterium Thermobifida fusca, exhibits a two-domain architecture resembling that of the disulfide oxidoreductases. The active site is located in a cleft at the domain interface. An arginine residue lays above the flavin ring in a position suited to stabilize the negatively charged flavin-peroxide and Criegee intermediates. This amino acid residue is predicted to exist in two positions; the "IN" position found in the crystal structure and an "OUT" position that allows NADPH to approach the flavin to reduce the cofactor. Domain rotations are proposed to bring about the conformational changes involved in catalysis. The structural studies highlight the functional complexity of this class of flavoenzymes, which coordinate the binding of three substrates (molecular oxygen, NADPH, and phenylacetone) in proximity of the flavin cofactor with formation of two distinct catalytic intermediates.

PubMed: 15328411
DOI: 10.1073/PNAS.0404538101

Experimental method

X-RAY DIFFRACTION (1.7 Å)