Molecular Structure of Paraoxonase-1 and Its Modifications in Relation to Enzyme Activity and Biological Functions-A Comprehensive Review.

PON1 is a Ca-dependent enzyme that indicates a hydrolytic activity towards a broad spectrum of substrates. The mechanism of hydrolysis catalyzed by this enzyme is poorly understood. It was shown that the active site of PON1 is highly dynamic. The catalytic center of this enzyme consists of side chains of amino acids binding two calcium ions, from which the first one performs a structural function and the other one is responsible for the catalytic properties of PON1. This review summarizes available information on the structure of PONs, the role of amino acids located in the active site in specificity, and multiple substrate affinity of enzymes for understanding and explaining the basis of the physiological function of PONs. Moreover, in this paper, we described the changes in the structure of PONs induced by environmental and genetic factors and their association with diseases. The detoxification efficiency depends on the polymorphism of the gene, especially Q192R. However, data on the association between single-nucleotide polymorphisms (SNPs) in the gene and cardiovascular or neurodegenerative diseases are insufficient. The reviewed papers may confirm that PON1 is a very promising tool for diagnostics, but further studies are required.