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J. Biol. Chem., Vol. 277, Issue 21, 18281-18290, May 24, 2002
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From the Lipid A (endotoxin) is a major structural
component of Gram-negative outer membranes. It also serves as the
hydrophobic anchor of lipopolysaccharide and is a potent activator of
the innate immune response. Lipid A molecules from the genus
Bordetella are reported to exhibit unusual structural
asymmetry with respect to the acyl chains at the 3- and 3'-positions.
These acyl chains are attached by UDP-N-acetylglucosamine
acyltransferase (LpxA). To determine the origin of the acyl
variability, the single lpxA ortholog present in each of
the genomes of Bordetella bronchiseptica (lpxABr), Bordetella parapertussis
(lpxAPa), and Bordetella
pertussis (lpxAPe) was cloned and expressed in Escherichia coli. In contrast to all LpxA proteins
studied to date, LpxABr and LpxAPe display
relaxed acyl chain length specificity in vitro, utilizing
C10OH-ACP, C12OH-ACP, and C14OH-ACP
at similar rates. Furthermore, hybrid lipid A molecules synthesized at
42 °C by an E. coli lpxA mutant complemented with
lpxAPe contain C10OH,
C12OH, and C14OH at both the 3- and
3'-positions, as determined by matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry. In contrast,
LpxA from B. parapertussis did not display relaxed
specificity but was selective for C10OH-ACP. This study
provides an enzymatic explanation for some of the unusual acyl chain
variations found in Bordetella lipid A.
Relaxed Acyl Chain Specificity of Bordetella
UDP-N-acetylglucosamine Acyltransferases*
,
Department of Biochemistry, Duke University
Medical Center, Durham, North Carolina 27710, the
§ Centre for Veterinary Science, Department of Clinical
Veterinary Medicine, University of Cambridge,
Cambridge CB3 0ES, United Kingdom, and the ¶ Middle Atlantic
Mass Spectrometry Facility, Department of Pharmacology and Molecular
Sciences, The Johns Hopkins University, Baltimore, Maryland 21205
*
This work was supported in part by National Institutes of
Health Grants GM51310 (to C. R. H. R.) and GM54882 (to R. J. C.), by National Institutes of Health Training Grant GM08558 in Biological Chemistry to Duke University (to C. R. S.), and by Wellcome Trust (UK) Program Grant 054588 (to D. J. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
919-684-5326; Fax: 919-684-8885; E-mail: raetz@biochem.duke.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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