Protein Domain : Paraoxonase1 IPR008363

Type	Family
Description	The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysisof 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 []. Mammals have 3 distinct paraoxonase types, termed PON1-3 [, ]. In mice andhumans, 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, onerequired for stability and one required for catalytic activity. The Ca2+ dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as theelectrophillic 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) []. Although PON2 has oxidative properties, theenzyme 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 [ ]. Rabbit and human serum PON1 also hydrolyse a variety of lactones and cycliccarbonate esters, including naturally occurring lactones and pharmacological agents []. Humans have 2 common PON1 allozymes, determined by the presenceof either arginine or glutamine at position 191. The A-type allozyme (glutamine at position 191) causes low paraoxonase activity []; thispolymorphism is associated with variations in cholesterol and lipoprotein levels.
Short Name	Paraoxonase1