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PDBsum entry 2gv8
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Oxidoreductase
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PDB id
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2gv8
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References listed in PDB file
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Key reference
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Title
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Mechanism of action of a flavin-Containing monooxygenase.
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Authors
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S.Eswaramoorthy,
J.B.Bonanno,
S.K.Burley,
S.Swaminathan.
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Ref.
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Proc Natl Acad Sci U S A, 2006,
103,
9832-9837.
[DOI no: ]
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PubMed id
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Abstract
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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 4alpha-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.
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Figure 2.
Fig. 2. Ribbon representation of the protein and
ball-and-stick model of FAD. The strand–turn–helix motifs
and the loop interlinking the two domains are labeled. FAD is in
the large domain and has no interaction with the small domain.
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Figure 4.
Fig. 4. Schematic representation of the functional
mechanism of FMO. Only the relevant parts required to explain
the function, isoalloxazine, nicotinamide, and methimazole, are
shown. Step 1 is seen in the wild type, step 3 is seen in the
protein–cofactor complex, and step 5 is seen in the
protein–methimazole complex structures.
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