Acyloxyacyl hydrolase

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acyloxyacyl hydrolase
Acyloxyacyl hydrolase heterodimer, Human
Identifiers
EC no.3.1.1.77
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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PMCarticles
PubMedarticles
NCBIproteins

The enzyme acyloxyacyl hydrolase (EC 3.1.1.77, AOAH) was discovered because it catalyzes the reaction

3-(acyloxy)acyl group of bacterial toxin + H2O = 3-hydroxyacyl group of bacterial toxin + a 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); 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 about 60 kDa that has two disulfide-linked subunits. The smaller subunit, of about 14 kDa (including glycosylation), is a member of the SAPLIP (saposin-like protein) family along with amoebapore, granulysin, acid sphingomyelinase, surfactant protein B, and the 4 sphingolipid activator proteins (saposins). The larger subunit, of 50 kDa, 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. PMC 7762960. PMID 33454018.