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Mechanism of action of a flavin-containing monooxygenase

Authors :
Eswaramoorthy, Subramaniam
Bonanno, Jeffrey B.
Burley, Stephen K.
Swaminathan, Subramanyam
Source :
Proceedings of the National Academy of Sciences of the United States. June 27, 2006, Vol. 103 Issue 26, p9832, 6 p.
Publication Year :
2006

Abstract

Elimination of nonnutritional and insoluble compounds is a critical task for any living organism. Flavin-containing monooxygenases (FMOs) attach an oxygen atom to the insoluble nucleophilic compounds to increase solubility and thereby increase excretion. Here we analyze the functional mechanism of FMO from Schizosaccharomyces pombe using the crystal structures of the wild type and protein-cofactor and protein-substrate complexes. The structure of the wild-type FMO revealed that the prosthetic group FAD is an integral part of the protein. FMO needs NADPH as a cofactor in addition to the prosthetic group for its catalytic activity. Structures of the protein-cofactor and protein-substrate complexes provide insights into mechanism of action. We propose that FMOs exist in the cell as a complex with a reduced form of the prosthetic group and NADPH cofactor, readying them to act on substrates. The 4[alpha]-hydroperoxyflavin form of the prosthetic group represents a transient intermediate of the monooxygenation process. The oxygenated and reduced forms of the prosthetic group help stabilize interactions with cofactor and substrate alternately to permit continuous enzyme turnover. three-dimensional structure | xenobiotics | methimazole

Details

Language :
English
ISSN :
00278424
Volume :
103
Issue :
26
Database :
Gale General OneFile
Journal :
Proceedings of the National Academy of Sciences of the United States
Publication Type :
Academic Journal
Accession number :
edsgcl.149023468