Acyloxyacyl hydrolase

acyloxyacyl hydrolase
Acyloxyacyl hydrolase heterodimer, Human
Identifiers
EC no.	3.1.1.77
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

In enzymology, an acyloxyacyl hydrolase (AOAH)(EC 3.1.1.77) is an enzyme that was discovered because it catalyzes the chemical reaction

3-(acyloxy)acyl group of bacterial lipopolysaccharide (lipid A moiety) ${\displaystyle \rightleftharpoons }$ 3-hydroxyacyl group of bacterial lipopolysaccharide + a fatty acid

Hence, this enzyme has one highly studied substrate, , and two products, [partially deacylated lipopolysaccharide] and fatty acid. It can also be a phospholipase A1 - A2, lysophospholipase, and acyl transferase.

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); the tetraacyl lipid A product can inhibit LPS signaling. Acyloxyacyl hydrolase is produced by monocyte-macrophages, neutrophils, dendritic cells, NK cells, ILC1 cells, and renal cortical tubule 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. Also see "AOAH".

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.
• Munford RS, Weiss JP, Lu M (2020). "Biochemical transformation of bacterial lipopolysaccharides by acyloxyacyl hydrolase reduces host injury and promotes recovery". J Biol Chem. 295 (51): 17842–1785. doi:10.1074/jbc.REV120.015254. PMID 33454018.