PON1 multitasks to protect health

The enzyme paraoxonase 1 (PON1) is an excellent example of a multitasking protein, displaying at least two very important functions: hydrolysis of organophosphorus (OP) anticholinesterases and prevention of oxidation of low density lipoproteins (LDLs) and high density lipoproteins (HDLs). PON1 is associated with the HDL particle and is a member of a family of calcium-dependent hydrolases (1). Interest in PON1 has escalated in recent years because of its two highly important roles, the first related to protection from OP compound poisoning from nerve agents (chemical warfare agents also used in terrorist attacks) and from agricultural insecticides, and the second related to protection against cardiovascular disease. The current study from the Furlong laboratory in this issue of PNAS (2) demonstrates the feasibility of producing in Escherichia coli recombinant human PON1 engineered to be more efficient catalytically toward several substrates than are the native human forms of PON1. This greater enzymatic efficiency offers promise of a potential catalytic therapeutic agent more effective than current therapies at saving lives and preserving health.