Acyloxyacyl hydrolase

In enzymology, an acyloxyacyl hydrolase (EC 3.1.1.77) is an enzyme that catalyzes the chemical reaction

3-(acyloxy)acyl group of bacterial lipopolysaccharide (lipid A moiety) 3-hydroxyacyl group of bacterial lipopolysaccharide + a fatty acid
acyloxyacyl hydrolase
Acyloxyacyl hydrolase heterodimer, Human
Identifiers
EC number3.1.1.77
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

Hence, this enzyme has one substrate, the 3-(acyloxy)acyl groups of bacterial lipopolysaccharides, and two products, [partially deacylated lipopolysaccharide] and fatty acid.

The enzyme removes from lipid A the secondary acyl chains that are needed for lipopolysaccharides to be recognized by the MD-2--TLR4 receptor on animal cells. This reaction inactivates the lipopolysaccharide (endotoxin). Acyloxyacyl hydrolase is produced by monocyte-macrophages, neutrophils, dendritic cells, and renal cortical epithelial cells. It is a protein of Mr = ~60,000 that has two disulfide-linked subunits. The smaller subunit, of Mr = ~14,000 (including glycosylation), is a member of the SAPLIP (saposin-like protein) family along with amoebopore, granulysin, acid sphingomyelinase, surfactant protein B, and the 4 sphingolipid activator proteins (saposins). The larger subunit, Mr = 50,000, contains the active site serine and the other elements of the His-Asp-Ser triad; AOAH is a GDSL lipase that has activity toward certain glycerolipids in addition to its presumed major in vivo substrate, LPS.

References

    • Erwin AL, Munford RS (1990). "Deacylation of structurally diverse lipopolysaccharides by human acyloxyacyl hydrolase". J. Biol. Chem. 265 (27): 16444–9. PMID 2398058.
    • Hagen, F.; O'Hara PJ, Munford RS; characterization of recombinant human acyloxyacyl hydrolase, a leukocyte enzyme that deacylates bacterial lipopolysaccharides (1991). "Expression". Biochemistry. 30 (34): 8415–8423. doi:10.1021/bi00098a020. PMID 1883828.
    • Munford RS, Hunter JP (1992). "Acyloxyacyl hydrolase, a leukocyte enzyme that deacylates bacterial lipopolysaccharides, has phospholipase, lysophospholipase, diacylglycerollipase, and acyltransferase activities in vitro". J. Biol. Chem. 267 (14): 10116–21. PMID 1577781.
    • Akoh CC, Lee GC, Shaw JF (2004). "GDSL family of serine esterases/lipases". Prog. Lipid. Res. 43: 534–552. doi:10.1016/j.plipres.2004.09.002. PMID 15522763.


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