3.1.8.2	evolution	the phosphotriesterase activity development between PON1, EC 3.1.8.1, and DFPase, EC 3.1.8.2, is investigated by using the hybrid density functional theory method B3LYP. Structure comparisons of evolutionarily related enzymes show that the mutation of Asn270 leads to the catalytic Ca2+ ion indirectly connecting the buried structural Ca2+ ion via hydrogen bonds in DFPase. It can reduce the plasticity of enzymatic structure, and possibly change the substrate preference from paraoxon (preferred substrate of PON1) to DFP (preferred substrate of DFPase), which implies an evolutionary transition from mono- to dinuclear catalytic centers, enzyme catalysis mechanism from an evolutionary perspective, overview	751626	
3.1.8.2	malfunction	insufficient organophosphate-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced organophosphate-hydrolyzing activity. Enzyme mutants show altered substrate specificity with increased activity against paraoxon and lactone substrates, overview	749628	
3.1.8.2	additional information	h-PON1 is a polymorphic enzyme. Molecular docking analysis, homology modelling, overview	749628	
3.1.8.2	additional information	in detoxification of nerve gas compounds or pesticides in the human body, due to non-human origin of the enzyme, immunological reactions occur when it is injected into body. In order to using DFPase as in vivo detoxifying agent, some manipulations to augment of its efficiency and to decrease of immunogenic problems are needed. Modifications such as PEGylation is one of the possible solutions to conquer these problems	750923	
3.1.8.2	additional information	organophosphorus hydrolase, OPH, contains a two-oxygen bridging mechanism in the active site suggesting subtle differences compared to organophosphorus acid anhydrolase, OPAA. OPAAs exhibit higher soman activities, whereas OPHs have higher activity against the organophosphorus pesticide paraoxon	-, 713896	
3.1.8.2	additional information	residue Asp229 plays a role in the coordination variation of calcium during the reaction. Quantum mechanical/molecular mechanical umbrella sampling simulations displays that the hydrolysis of diisopropyl fluorophosphate (DFP) and (S)-sarin processes by DFPase presents two different reaction pathways involving nucleophilic attack by Asp229 or an activated water on phosphorus. Modeling of active site and reaction mechanism with nucleophile Asp229 and coordinating Ca2+, detailed overview. Optimized geometries for the intermediates, transition state, and product for the hydrolysis step of DFPase	752291, 755573	
3.1.8.2	additional information	the metal-substituted catalysts generates the activated water molecules that initiate nucleophilic attack on the phosphorus atom of the substrate, resulting in the cleavage of phosphoester bond and the release of leaving group	751964	
3.1.8.2	additional information	the OPAA structure is composed of two domains, amino and carboxy domains, with the latter exhibiting a pita bread architecture and harboring the active site with the binuclear Mn2+ ions. The native enzyme structure reveals the presence of a well-defined nonproteinaceous density in the active site, which might be due to a bound glycolate, which is isosteric with a glycine product. All three glycolate oxygens coordinate the two Mn2+ atoms	-, 707530	
3.1.8.2	additional information	the phosphotriesterase diisopropyl fluorophosphatase (DFPase) is a calcium-dependent beta-propeller protein. PON1, EC 3.1.8.1, and DFPase, EC 3.1.8.2, seem to employ similar catalytic mechanisms as phosphotriesterase, due to their structural similarities of active sites. The attacking nucleophile for phosphotriester hydrolysis is identified to be an activated water molecule, with the nucleophile attacking the phosphorus center. The E53Q and D269N mutants in PON1 both possess measurable lactonase and paraoxonase activity, and mutation studies combined with related molecular dynamics simulations suggest that the water activated by Glu53 and Asp269 is the most likely attacking nucleophile. Analysis of the rate-determining reaction step of the organophosphorus compound hydrolysis catalyzed both by DFPase and PON1. Structure-function relationship, overview. Active site structure of DFPase (PDB ID 2GVW) and substrate docking	751626	
3.1.8.2	physiological function	diisopropyl fluorophosphatase is a calcium-dependent phosphotriesterase that acts on a variety of highly toxic organophosphorus compounds, that act as inhibitors of acetylcholinesterase	713615	
3.1.8.2	physiological function	human paraoxonase 1 (h-PON1) is a serum enzyme that can hydrolyze a variety of substrates, including organophosphate (OP) compounds. PON1 can hydrolyze and inactivate a variety of organophosphate (OP) compounds, including certain OP pesticides and nerve agents (NAs). It is a potential candidate for the development of antidote against OP poisoning in humans. The enzyme possesses anti-inflammatory, anti-oxidative, anti-diabetic and quorum sensor-hydrolyzing activities, it is proposed that the lactonase activity of the enzyme is important for these defensive roles, cf. EC 3.1.1.81	749628	
3.1.8.2	physiological function	the enzyme efficiently catalyze the hydrolysis of the substrate diisopropyl fluorophosphate and a wide range of organophosphorus nerve agents, including soman, sarin, and tabun	752291, 755573	
3.1.8.2	physiological function	the squid phosphotriesterase diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris shows relatively specific substrate preference, efficiently catalyzing the hydrolysis of diisopropyl fluorophosphate (DFP) and G-type nerve agents, including tabun (GA), sarin (GB), soman (GD), and cyclohexyl sarin (GF). The detoxification of the organophosphorous (OP) agent is achieved by the hydrolytic reaction producing a phosphate or phosphonate and a fluoride ion	751626