Covalent structure of liver microsomal flavin-containing monooxygenase form 1
Liver microsomal, flavin-containing monooxygenases catalyze NADPH- and oxygen-dependent oxidation of a wide variety of antipsychotic and narcotic drugs. Two forms of these enzymes have been isolated and partially characterized (Ozols, J. (1989) Biochem. Biophys. Res. Commun. 163, 49-55). The amino a...
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Published in | The Journal of biological chemistry Vol. 265; no. 18; pp. 10289 - 10299 |
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Main Author | |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Biochemistry and Molecular Biology
25.06.1990
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Subjects | |
Online Access | Get full text |
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Summary: | Liver microsomal, flavin-containing monooxygenases catalyze NADPH- and oxygen-dependent oxidation of a wide variety of antipsychotic
and narcotic drugs. Two forms of these enzymes have been isolated and partially characterized (Ozols, J. (1989) Biochem. Biophys.
Res. Commun. 163, 49-55). The amino acid sequence of form 1 is presented here. Sequence determination has been achieved by
automated Edman degradation of peptides generated by chemical and enzymatic cleavages. The NH2 terminus of form 1 oxygenase
is blocked. Partial acid hydrolysis of the blocked peptides removed acetyl groups and permitted their analysis by Edman degradation.
Form 1 monooxygenase contains 536 residues. A peptide of 32 residues at the COOH terminus of the protein could not be sequenced
in a gas-phase or pulsed liquid-phase sequenator, due to its extreme hydrophobicity. Covalent coupling of this peptide to
an aryl amine membrane by means of carbodiimide, followed by automated solid-phase sequencing, established the order of 30
amino acid residues. The hydrophobic segment at the COOH terminus presumably functions to anchor the monooxygenase to the
microsomal membrane. The amino acid sequence of form 1 monooxygenase, despite overlapping substrate specificity, is not related
to the cytochrome P-450 superfamily. Comparison of the sequence of form 1 oxygenase with other known sequences, except for
some short segments similar to those in the bacterial flavin-containing monooxygenases, did not reveal significant sequence
similarities that would suggest a structural or evolutionary relationship. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)86945-9 |