| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, June 5, 1996, and in revised form, July 29, 1996)
From the The first enzyme of lipid A assembly in
Escherichia coli is an acyltransferase that attaches an
R-3-hydroxymyristoyl moiety to UDP-GlcNAc at the GlcNAc
3-OH. This reaction is reversible and thermodynamically unfavorable.
The subsequent deacetylation of the product,
UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc, is
therefore the first committed step of lipid A biosynthesis. We now
demonstrate that inhibition of either the acyltransferase or the
deacetylase in living cells results in a 5-10-fold increase in the
specific activity of the deacetylase in extracts prepared from such
cells. Five other enzymes of the lipid A pathway are not affected. The
elevated specific activity of deacetylase observed in extracts of lipid
A-depleted cells is not accompanied by a significant change in the
Km for the substrate, but is mainly an effect on
Vmax. Western blots demonstrate that more
deacetylase protein is indeed made. However, deacetylase messenger RNA
levels are not significantly altered. Inhibition of lipid A
biosynthesis must either stimulate the translation of available
mRNA or slow the turnover of pre-existing deacetylase. In contrast,
inhibition of 3-deoxy-D-manno-octulosonic acid
(Kdo) biosynthesis has no effect on deacetylase specific activity. The
underacylated lipid A-like disaccharide precursors that accumulate
during inhibition of Kdo formation may be sufficient to exert normal
feedback control.
Volume 271, Number 42,
Issue of October 18, 1996
pp. 25898-25905
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
THE SECOND ENZYMATIC STEP OF LIPID A BIOSYNTHESIS
,
,
Department of Biochemistry, Duke University
Medical Center, Durham, North Carolina 27710, the ¶ Department
of Microbiology, University of Kansas Medical Center, Kansas City,
Kansas 66103, and the Departments of 
Antibiotic Discovery
and Development and '' Enzymology, Merck Research Laboratories,
Rahway, New Jersey 07065
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. E. Mdluli, P. R. Witte, T. Kline, A. W. Barb, A. L. Erwin, B. E. Mansfield, A. L. McClerren, M. C. Pirrung, L. N. Tumey, P. Warrener, et al. Molecular Validation of LpxC as an Antibacterial Drug Target in Pseudomonas aeruginosa. Antimicrob. Agents Chemother., June 1, 2006; 50(6): 2178 - 2184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Doerrler and C. R. H. Raetz Loss of Outer Membrane Proteins without Inhibition of Lipid Export in an Escherichia coli YaeT Mutant J. Biol. Chem., July 29, 2005; 280(30): 27679 - 27687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hernick, H. A. Gennadios, D. A. Whittington, K. M. Rusche, D. W. Christianson, and C. A. Fierke UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine Deacetylase Functions through a General Acid-Base Catalyst Pair Mechanism J. Biol. Chem., April 29, 2005; 280(17): 16969 - 16978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Vorachek-Warren, S. M. Carty, S. Lin, R. J. Cotter, and C. R. H. Raetz An Escherichia coli Mutant Lacking the Cold Shock-induced Palmitoleoyltransferase of Lipid A Biosynthesis. ABSENCE OF UNSATURATED ACYL CHAINS AND ANTIBIOTIC HYPERSENSITIVITY AT 12 {degrees}C J. Biol. Chem., April 12, 2002; 277(16): 14186 - 14193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Allan, C. L. Clayton, A. McLaren, D. M. Wallace, and B. W. Wren Characterization of the low-pH responses of Helicobacter pylori using genomic DNA arrays Microbiology, August 1, 2001; 147(8): 2285 - 2292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gronow and H. Brade Invited review: Lipopolysaccharide biosynthesis: which steps do bacteria need to survive? Innate Immunity, February 1, 2001; 7(1): 3 - 23. [Abstract] [PDF]
|
|
|
|
 |
|
 N. R. Stanley, K. Findlay, B. C. Berks, and T. Palmer Escherichia coli Strains Blocked in Tat-Dependent Protein Export Exhibit Pleiotropic Defects in the Cell Envelope J. Bacteriol., January 1, 2001; 183(1): 139 - 144. [Abstract] [Full Text]
|
|
|
|
|
|
T. J. O. Wyckoff and C. R. H. Raetz The Active Site of Escherichia coli UDP-N-acetylglucosamine Acyltransferase. CHEMICAL MODIFICATION AND SITE-DIRECTED MUTAGENESIS J. Biol. Chem., September 17, 1999; 274(38): 27047 - 27055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Carty, K. R. Sreekumar, and C. R. H. Raetz Effect of Cold Shock on Lipid A Biosynthesis in Escherichia coli. INDUCTION AT 12 °C OF AN ACYLTRANSFERASE SPECIFIC FOR PALMITOLEOYL-ACYL CARRIER PROTEIN J. Biol. Chem., April 2, 1999; 274(14): 9677 - 9685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Dotson, I. A. Kaltashov, R. J. Cotter, and C. R. H. Raetz Expression Cloning of a Pseudomonas Gene Encoding a Hydroxydecanoyl-Acyl Carrier Protein-Dependent UDP-GlcNAc Acyltransferase J. Bacteriol., January 15, 1998; 180(2): 330 - 337. [Abstract] [Full Text]
|
|
|
|
|
|
T. J. Odegaard, I. A. Kaltashov, R. J. Cotter, L. Steeghs, P. van der Ley, S. Khan, D. J. Maskell, and C. R. H. Raetz Shortened Hydroxyacyl Chains on Lipid A of Escherichia coli Cells Expressing a Foreign UDP-N-Acetylglucosamine O-Acyltransferase J. Biol. Chem., August 8, 1997; 272(32): 19688 - 19696. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
