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J Biol Chem, Vol. 273, Issue 46, 30599-30607, November 13, 1998
From the Flavin-containing monooxygenases
(FMOs) are NADPH-dependent flavoenzymes that catalyze
the oxidation of heteroatom centers in numerous drugs and xenobiotics.
FMO2, or "pulmonary" FMO, one of five forms of the enzyme
identified in mammals, is expressed predominantly in lung and differs
from other FMOs in that it can catalyze the N-oxidation of
certain primary alkylamines. We describe here the isolation and
characterization of cDNAs for human FMO2. Analysis of the sequence
of the cDNAs and of a section of the corresponding gene revealed
that the major FMO2 allele of humans encodes a polypeptide
that, compared with the orthologous protein of other mammals, lacks 64 amino acid residues from its C terminus. Heterologous expression of the
cDNA revealed that the truncated polypeptide was catalytically
inactive. The nonsense mutation that gave rise to the truncated
polypeptide, a C
The Flavin-containing Monooxygenase 2 Gene (FMO2)
of Humans, but Not of Other Primates, Encodes a Truncated,
Nonfunctional Protein
,
,
,
Laboratory of Molecular Biology, Department
of Biochemistry, Queen Mary and Westfield College, University of
London, London E1 4NS, United Kingdom, the ¶ Department of
Biochemistry and Molecular Biology, University College London,
London WC1E 6BT, United Kingdom, and ** Molecular Toxicology, Imperial
College School of Medicine, London W2 1PG, United Kingdom
T transition in codon 472, is not present in the
FMO2 gene of closely related primates, including gorilla
and chimpanzee, and must therefore have arisen in the human lineage
after the divergence of the Homo and Pan clades. Possible mechanisms
for the fixation of the mutation in the human population and the
potential significance of the loss of functional FMO2 in humans are discussed.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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