Human plasma paraoxonase (PON1) is a calcium-dependent organophosphate-hydrolase. In plasma, PON1 is bound to high-density lipoproteins (HDL). PON1 prevents the oxidation of LDL and scavenges oxidized phospholipids, thus protecting from atherogenesis. Improving the prophylaxis and treatment of organophosphate (OP) poisoning is a public health concern that also interests the civilian safety and the military. In this context, engineering and formulation of enzymes able to scavenge or hydrolyze OPs, such as PON1, are widely studied. Determination of the PON1 three-dimensional structure is a key step toward improvement of the enzyme functional properties.