Expression and Characterization of Recombinant Human Acyloxyacyl Hydrolase, a Leukocyte Enzyme That Deacylates Bacterial Lipopolysaccharides

Frederick S. Hagen, Francis J. Grant, Joseph L. Kuijper, Patrick J. O’Hara, Clive A. Slaughter, Carolyn R. Moomaw, Kim Orth, Robert S. Munford

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The molecular cloning and eukaryotic cell expression of the complementary DNA for human neutrophil acyloxyacyl hydrolase (AOAH) are described. AOAH is a leukocyte enzyme that selectively removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (endotoxins), thereby detoxifying the molecules. The two disulfide-linked subunits of the enzyme are encoded by a single mRNA. The amino acid sequence of the protein contains a lipase consensus sequence in the large subunit and a region in the small subunit that is similar to the saposins, cofactors for sphingolipid hydrolases. The recombinant enzyme, like native AOAH, hydrolyzes secondary acyl chains from more than one position on the lipopolysaccharide backbone. Acyloxyacyl hydrolase is a novel two-component lipase that, by deacylating lipopolysaccharides, may modulate host inflammatory responses to Gram-negative bacterial invasion.

Original languageEnglish (US)
Pages (from-to)8415-8423
Number of pages9
JournalBiochemistry
Volume30
Issue number34
DOIs
StatePublished - Aug 1 1991
Externally publishedYes

Fingerprint

Lipopolysaccharides
Leukocytes
Enzymes
Lipase
Saposins
Lipid A
Sphingolipids
Cloning
Consensus Sequence
Molecular Cloning
Eukaryotic Cells
Hydrolases
Endotoxins
Disulfides
Amino Acid Sequence
Neutrophils
Complementary DNA
Amino Acids
Messenger RNA
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Expression and Characterization of Recombinant Human Acyloxyacyl Hydrolase, a Leukocyte Enzyme That Deacylates Bacterial Lipopolysaccharides. / Hagen, Frederick S.; Grant, Francis J.; Kuijper, Joseph L.; O’Hara, Patrick J.; Slaughter, Clive A.; Moomaw, Carolyn R.; Orth, Kim; Munford, Robert S.

In: Biochemistry, Vol. 30, No. 34, 01.08.1991, p. 8415-8423.

Research output: Contribution to journalArticle

Hagen, Frederick S. ; Grant, Francis J. ; Kuijper, Joseph L. ; O’Hara, Patrick J. ; Slaughter, Clive A. ; Moomaw, Carolyn R. ; Orth, Kim ; Munford, Robert S. / Expression and Characterization of Recombinant Human Acyloxyacyl Hydrolase, a Leukocyte Enzyme That Deacylates Bacterial Lipopolysaccharides. In: Biochemistry. 1991 ; Vol. 30, No. 34. pp. 8415-8423.
@article{ef8d69bfa5254afca3fb778e8b5f647c,
title = "Expression and Characterization of Recombinant Human Acyloxyacyl Hydrolase, a Leukocyte Enzyme That Deacylates Bacterial Lipopolysaccharides",
abstract = "The molecular cloning and eukaryotic cell expression of the complementary DNA for human neutrophil acyloxyacyl hydrolase (AOAH) are described. AOAH is a leukocyte enzyme that selectively removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (endotoxins), thereby detoxifying the molecules. The two disulfide-linked subunits of the enzyme are encoded by a single mRNA. The amino acid sequence of the protein contains a lipase consensus sequence in the large subunit and a region in the small subunit that is similar to the saposins, cofactors for sphingolipid hydrolases. The recombinant enzyme, like native AOAH, hydrolyzes secondary acyl chains from more than one position on the lipopolysaccharide backbone. Acyloxyacyl hydrolase is a novel two-component lipase that, by deacylating lipopolysaccharides, may modulate host inflammatory responses to Gram-negative bacterial invasion.",
author = "Hagen, {Frederick S.} and Grant, {Francis J.} and Kuijper, {Joseph L.} and O’Hara, {Patrick J.} and Slaughter, {Clive A.} and Moomaw, {Carolyn R.} and Kim Orth and Munford, {Robert S.}",
year = "1991",
month = "8",
day = "1",
doi = "10.1021/bi00098a020",
language = "English (US)",
volume = "30",
pages = "8415--8423",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "34",

}

TY - JOUR

T1 - Expression and Characterization of Recombinant Human Acyloxyacyl Hydrolase, a Leukocyte Enzyme That Deacylates Bacterial Lipopolysaccharides

AU - Hagen, Frederick S.

AU - Grant, Francis J.

AU - Kuijper, Joseph L.

AU - O’Hara, Patrick J.

AU - Slaughter, Clive A.

AU - Moomaw, Carolyn R.

AU - Orth, Kim

AU - Munford, Robert S.

PY - 1991/8/1

Y1 - 1991/8/1

N2 - The molecular cloning and eukaryotic cell expression of the complementary DNA for human neutrophil acyloxyacyl hydrolase (AOAH) are described. AOAH is a leukocyte enzyme that selectively removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (endotoxins), thereby detoxifying the molecules. The two disulfide-linked subunits of the enzyme are encoded by a single mRNA. The amino acid sequence of the protein contains a lipase consensus sequence in the large subunit and a region in the small subunit that is similar to the saposins, cofactors for sphingolipid hydrolases. The recombinant enzyme, like native AOAH, hydrolyzes secondary acyl chains from more than one position on the lipopolysaccharide backbone. Acyloxyacyl hydrolase is a novel two-component lipase that, by deacylating lipopolysaccharides, may modulate host inflammatory responses to Gram-negative bacterial invasion.

AB - The molecular cloning and eukaryotic cell expression of the complementary DNA for human neutrophil acyloxyacyl hydrolase (AOAH) are described. AOAH is a leukocyte enzyme that selectively removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (endotoxins), thereby detoxifying the molecules. The two disulfide-linked subunits of the enzyme are encoded by a single mRNA. The amino acid sequence of the protein contains a lipase consensus sequence in the large subunit and a region in the small subunit that is similar to the saposins, cofactors for sphingolipid hydrolases. The recombinant enzyme, like native AOAH, hydrolyzes secondary acyl chains from more than one position on the lipopolysaccharide backbone. Acyloxyacyl hydrolase is a novel two-component lipase that, by deacylating lipopolysaccharides, may modulate host inflammatory responses to Gram-negative bacterial invasion.

UR - http://www.scopus.com/inward/record.url?scp=0026015327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026015327&partnerID=8YFLogxK

U2 - 10.1021/bi00098a020

DO - 10.1021/bi00098a020

M3 - Article

VL - 30

SP - 8415

EP - 8423

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 34

ER -