Literature summary for 3.1.8.1 extracted from

Aggarwal, G.; Prajapati, R.; Tripathy, R.K.; Bajaj, P.; Iyengar, A.R.; Sangamwar, A.T.; Pande, A.H.
Toward understanding the catalytic mechanism of human paraoxonase 1 site-specific mutagenesis at position 192 (2016), PLoS ONE, 11, e0147999 .

Cloned(Commentary)

Cloned (Comment)	Organism
gene PON1, sequence comparisons, recombinant expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3), mutants H115W/R192H and H115W/R192M are expressed as truncated proteins, subcloning in Escherichia coli strain DH5alpha	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
H115W/R192A	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192D	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192E	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192F	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192G	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192H	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192I	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192K	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192L	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192M	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192N	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192P	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192Q	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192R	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192S	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192T	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192V	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192W	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
H115W/R192Y	site-directed mutagenesis, the mutant shows altered substrate specificity and activity compared to the wild-type, overview	Homo sapiens
R192A	site-directed mutagenesis	Homo sapiens
R192I	site-directed mutagenesis	Homo sapiens
R192K	site-directed mutagenesis	Homo sapiens
R192Q	site-directed mutagenesis	Homo sapiens
R192V	site-directed mutagenesis	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.5	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192N	Homo sapiens
0.9	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192I	Homo sapiens
0.9	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192K	Homo sapiens
0.9	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutants H115W	Homo sapiens
1.1	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192S	Homo sapiens
1.2	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant wild-type enzyme	Homo sapiens
1.2	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192A	Homo sapiens
1.3	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192W	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
extracellular	-	Homo sapiens	-	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Ca2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
dimethyl-paraoxon + H2O	Homo sapiens	-	dimethyl phosphate + 4-nitrophenol	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P27169	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by isolating inclusion bodies, refolding of the proteins, and anion exchange chromatography	Homo sapiens

Renatured (Commentary)

Renatured (Comment)	Organism
refolding of recombinant wild-type and mutant enzymes from inclusion bodies in Escherichia coli strain BL21(DE3) by 8 M urea	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
serum	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
diethyl (3,5,6-trichloropyridin-2-yl) phosphate + H2O	i.e. chlorpyrifos-oxon or CPO	Homo sapiens	?	-	?
diisopropyl fluorophosphate + H2O	reaction of EC 3.1.8.2	Homo sapiens	diisopropyl phosphate + fluoride	-	?
dimethyl-paraoxon + H2O	-	Homo sapiens	dimethyl phosphate + 4-nitrophenol	-	?
additional information	human paraoxonase 1 (h-PON1) can hydrolyze a variety of substrates. Interaction of recombinant PON1 proteins with lactones, overview	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
More	cf. EC 3.1.8.2	Homo sapiens
paraoxonase 1	-	Homo sapiens
PON1	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
25	-	assay at	Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
0.1	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192I	Homo sapiens
0.2	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192S	Homo sapiens
0.9	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant wild-type enzyme	Homo sapiens
3.8	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192N	Homo sapiens
4.2	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192W	Homo sapiens
6	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutants H115W	Homo sapiens
7.7	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192A	Homo sapiens
10.7	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192K	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
8	-	assay at	Homo sapiens

General Information

General Information	Comment	Organism
additional information	enzyme struture homology modelling, overview	Homo sapiens
physiological function	The enzyme exhibits anti-inflammatory, anti-oxidative, anti-atherogenic, anti-diabetic, anti-microbial and organophosphate-hydrolyzing activities	Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism
0.11	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192I	Homo sapiens
0.18	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192S	Homo sapiens
0.75	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant wild-type enzyme	Homo sapiens
3.23	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192W	Homo sapiens
6.42	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192A	Homo sapiens
6.67	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutants H115W	Homo sapiens
7.6	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192N	Homo sapiens
11.89	-	dimethyl-paraoxon	pH 8.0, 25°C, recombinant mutant H115W/R192K	Homo sapiens