Short name: Paraoxonase2
Overlapping homologous superfamilies
- Six-bladed beta-propeller, TolB-like (IPR011042)
- Arylesterase (IPR002640)
- Paraoxonase2 (IPR008364)
The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysis of the toxic metabolites of a variety of organophosphorus insecticides. The enzymes hydrolyse a broad spectrum of organophosphate substrates, including paraoxon and a number of aromatic carboxylic acid esters (e.g., phenyl acetate), and hence confer resistance to organophosphate toxicity [PMID: 8661009].
Mammals have 3 distinct paraoxonase types, termed PON1-3 [PMID: 8661009, PMID: 11038162]. In mice and humans, the PON genes are found on the same chromosome in close proximity. PON activity has been found in variety of tissues, with highest levels in liver and serum - the source of serum PON is thought to be the liver. Unlike mammals, fish and avian species lack paraoxonase activity.
Human and rabbit PONs appear to have two distinct Ca2+ binding sites, one required for stability and one required for catalytic activity. The Ca2+ dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as the electrophillic catalyst, like that proposed for phospholipase A2. The paraoxonase enzymes, PON1 and PON3, are high density lipoprotein (HDL)- associated proteins capable of preventing oxidative modification of low density lipoproteins (LPL) [PMID: 11038162]. Although PON2 has oxidative properties, the enzyme does not associate with HDL.
Within a given species, PON1, PON2 and PON3 share ~60% amino acid sequence identity, whereas between mammalian species particular PONs (1,2 or 3) share 79-90% identity at the amino acid level. Human PON1 and PON3 share numerous conserved phosphorylation and N-glycosylation sites; however, it is not known whether the PON proteins are modified at these sites, or whether modification at these sites is required for activity in vivo [PMID: 11038162].
- PR01787 (PARAOXONASE2)