Information on EC 3.1.1.25 - 1,4-lactonase and Organism(s) Homo sapiens and UniProt Accession Q15165

Ascorbate and aldarate metabolism, Galactose metabolism

-

702421, 709261

lactonase, gamma

-

hydrolysis of carboxylic ester

-

KEGG

-

1,4-lactone hydroxyacylhydrolase

The enzyme is specific for 1,4-lactones with 4-8 carbon atoms. It does not hydrolyse simple aliphatic esters, acetylcholine, sugar lactones or substituted aliphatic lactones, e.g. 3-hydroxy-4-butyrolactone; requires Ca2+.

37278-38-9

-

2-coumaranone + H2O

(2-hydroxyphenyl)acetic acid

-

-

?

5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid 1,5-lactone + H2O

5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid

-

-

?

dihydrocoumarin + H2O

3-(2-hydroxyphenyl)propanoic acid

-

-

?

DL-3-oxo-hexanoylhomoserine lactone + H2O

DL-3-oxo-hexanoylhomoserine

-

-

?

DL-dodecanoylhomoserine lactone + H2O

DL-dodecanoylhomoserine

-

-

?

DL-heptanoylhomoserine lactone + H2O

DL-heptanoylhomoserine

-

-

?

DL-tetradecanoylhomoserine lactone + H2O

DL-tetradecanoylhomoserine

-

-

?

gamma-phenyl-gamma-butyrolactone + H2O

4-hydroxy-4-phenylbutanoic acid

-

-

?

(1R,5S)-oxabicyclooctenone + H2O

?

(1S,5R)-oxabicyclooctenone + H2O

?

(R)-alpha-hydroxy-gamma-butyrolactone + H2O

(R)-2-hydroxybutyric acid

enzyme variant Q192: 0.88% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 3.95% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

(R)-dihydro-5-(hydroxymethyl)-2(3H)-furanone + H2O

?

enzyme variant Q192: 1.23% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 3.29% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

(R)-gamma-valerolactone + H2O

4-hydroxypentanoic acid

-

-

?

(S)-alpha-hydroxy-gamma-butyrolactone + H2O

(S)-2-hydroxybutyric acid

enzyme variant Q192: 8.14% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 19.6% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

(S)-beta-hydroxy-gamma-butyrolactone + H2O

(S)-3-hydroxybutyric acid

enzyme variant Q192: 0.6% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 0.76% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

(S)-dihydro-5-(hydroxymethyl)-2(3H)-furanone + H2O

?

enzyme variant Q192: 0.78% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 1.12% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

1,3-benzoxazol-2-one + H2O

?

-

-

?

2-coumaranone + H2O

(2-hydroxyphenyl)acetic acid

3-hydroxyoctanoate + H2O

?

-

-

?

4-(1-propenyloxymethyl)-1,3-dioxolan-2-one + H2O

?

enzyme variant Q192: 2.23% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 2.52% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

4-methoxyphenyl acetate + H2O

4-methoxyphenol + acetate

-

-

?

5-(thiobutyl)butyrolactone + H2O

?

the lactonase and the esterase activity of PON1 is mediated by the His115-His134

-

?

5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid 1,5-lactone + H2O

5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid

-

-

?

5-thiobutyl butyrolactone + H2O

4-(butylsulfanyl)-4-hydroxybutanoic acid

-

-

?

7-O-diethyl phosphoryl 3-cyano 4-methyl 7-hydroxycoumarin + H2O

?

-

681264

-

?

7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin + H2O

(2Z)-2-cyano-3-[4-[(diethoxyphosphoryl)oxy]-2-hydroxyphenyl]but-2-enoic acid

-

-

?

alpha-angelica lactone + H2O

?

-

-

?

alpha-angelicalactone + H2O

4-hydroxy-pent-3-enoic acid

-

-

?

alpha-angelicalactone + H2O

4-hydroxypent-3-enoic acid

-

-

?

alpha-angelicalactone + H2O

?

enzyme variant Q192: 19.9% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 14.8% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

alpha-bromo-gamma-butyrolactone + H2O

2-bromobutyric acid

enzyme variant Q192: 47.2% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 40.8% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

beta-hydroxybutyrolactone + H2O

?

canrenone + H2O

?

not hydrolyzed by PON1 (P27169 (UniProt)) and PON2 (Q15165 (UniProt))

-

?

delta valerolactone + H2O

5-hydroxypentanoic acid

-

-

?

delta-decanolactone + H2O

5-hydroxydecanoic acid

delta-decanolactone + H2O

?

-

-

?

delta-dodecanolactone + H2O

?

-

-

?

delta-hexalactone + H2O

5-hydroxyhexanoic acid

-

-

?

delta-hexalactone + H2O

?

-

-

?

delta-nonalactone + H2O

5-hydroxynonanoate

-

-

?

delta-nonalactone + H2O

5-hydroxynonanoic acid

delta-tetradecanolactone + H2O

5-hydroxytetradecanoic acid

-

-

?

delta-undecanolactone + H2O

5-hydroxyundecanoic acid

-

-

?

delta-undecatiolactone + H2O

?

-

-

?

delta-valerolactone + H2O

5-hydroxypentanoic acid

5 entries

delta-valerolactone + H2O

?

dihydrocoumarin + H2O

3-(2-hydroxyphenyl)-propionic acid

dihydrocoumarin + H2O

3-(2-hydroxyphenyl)propanoic acid

6 entries

DL-3-oxo-hexanoyl-homoserine lactone + H2O

DL-3-oxo-hexanoyl-homoserine

-

-

?

DL-dodecanoyl-homoserine lactone + H2O

DL-dodecanoyl-homoserine

-

-

?

DL-dodecanoylhomoserine lactone + H2O

DL-dodecanoylhomoserine

-

-

?

DL-heptanoyl-homoserine lactone + H2O

DL-heptanoyl-homoserine

-

-

?

DL-heptanoylhomoserine lactone + H2O

DL-heptanoylhomoserine

-

-

?

DL-tetradecanoyl-homoserine lactone + H2O

DL-tetradecanoyl-homoserine

-

-

?

DL-tetradecanoylhomoserine lactone + H2O

DL-tetradecanoyl-homoserine

-

-

?

epsilon-caprolactone + H2O

6-hydroxyhexanoic acid

enzyme variant Q192: 14.8% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 25.7% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

epsilon-caprolactone + H2O

?

-

-

?

ethyl acetate + H2O

ethanol + acetate

-

-

?

gamma -nonalactone + H2O

?

-

-

?

gamma-butyrolactone + H2O

4-hydroxy-butyric acid

-

-

?

gamma-butyrolactone + H2O

4-hydroxybutanoate

-

-

?

gamma-butyrolactone + H2O

4-hydroxybutanoic acid

-

664111, 691230

-

?

gamma-butyrolactone + H2O

4-hydroxybutyric acid

gamma-butyrolactone + H2O

?

-

-

?

gamma-butyrolactone + H2O

gamma-hydroxybutyrate

-

94285, 94286

-

r

gamma-caprolactone + H2O

4-hydroxyhexanoic acid

-

664111, 665745

-

?

gamma-caprolactone + H2O

gamma-hydroxycaproate

gamma-decanolactone + H2O

4-hydroxydecanoic acid

gamma-decanolactone + H2O

?

-

-

?

gamma-dodecanoic acid lactone + H2O

4-hydroxydodecanoic acid

-

-

?

gamma-dodecanoic lactone + H2O

4-hydroxydodecanoic acid

-

664064

-

?

gamma-heptalactone + H2O

4-hydroxyheptanoic acid

-

-

?

gamma-heptalactone + H2O

?

-

-

?

gamma-heptanolide + H2O

4-hydroxyheptanoic acid

-

-

?

gamma-hexalactone + H2O

4-hydroxyhexanoic acid

-

-

?

gamma-hexalactone + H2O

?

-

-

?

gamma-nonalactone + H2O

4-hydroxynonanoic acid

gamma-nonanoic acid lactone + H2O

4-hydroxynonanoic acid

-

-

?

gamma-octalactone + H2O

4-hydroxyoctanoate

gamma-octalactone + H2O

4-hydroxyoctanoic acid

-

-

?

gamma-octalactone + H2O

?

-

-

?

gamma-phenyl-gamma-butyrolactone + H2O

4-hydroxy-4-phenyl-butanoic acid

-

-

?

gamma-phenyl-gamma-butyrolactone + H2O

4-hydroxy-4-phenylbutanoic acid

-

-

?

gamma-thiobutyrolactone + H2O

?

-

-

?

gamma-undecanoic acid lactone + H2O

4-hydroxyundecanoic acid

-

-

?

gamma-undecanolactone + H2O

4-hydroxyundecanoic acid

-

-

?

gamma-undecanolactone + H2O

?

gamma-valerolactone + H2O

4-hydroxypentanoic acid

gamma-valerolactone + H2O

?

-

-

?

gamma-valerolactone + H2O

gamma-hydroxyvalerate

homocysteine thiolactone + H2O

?

-

715735, 750511

-

?

homocysteinethiolactone + H2O

homocysteine

-

-

?

homocysteinthiolactone + H2O

(2S)-2-aminobutanethioic S-acid

-

-

?

homogenestic acid lactone + H2O

?

-

-

?

homogentisic acid lactone + H2O

homogentisic acid

lovastatin + H2O

?

mevastatin + H2O

?

activity with enzyme variant Q192 and R192

-

?

N-oxodecanoyl-DL-homoserine lactone + H2O

N-(3-oxodecanoyl)homoserine

-

-

?

N-oxododecanoyl-DL-homoserine lactone + H2O

?

-

-

?

pantoyl lactone + H2O

2,4-dihydroxy-3,3-dimethylbutanoic acid

-

-

?

phenyl acetate + H2O

?

-

670788

-

?

propylene carbonate + H2O

?

enzyme variant Q192: 5.02% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 8.8% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

simvastatin + H2O

?

activity with enzyme variant Q192 and R192

-

?

spironolactone + H2O

?

thiobutyl butyrolactone + H2O

?

-

692732

-

?

undecano-gamma-lactone + H2O

4-hydroxyundecanoic acid

enzyme variant Q192: 11.8% of the activity with phenyl acetate (cf. EC 3.1.1.2), enzyme variant R192: 12.7% of the activity with phenyl acetate (cf. EC 3.1.1.2)

-

?

additional information

?

-

18 entries

homocysteine thiolactone + H2O

?

-

715735

-

?

additional information

?

-

Ca2+

2-hydroxyquinoline

ascorbate

-

ascorbate/Cu2+ system is the most potent in inactivating the lactonase activity (by 90%). Cu2+ remarkably enhances the inactivation in the presence of ascorbate. Ascorbate/Cu2+ (0.5 mM/0.001 mM) system shows ca. 95% inactivation. Ascorbate/Cu2+-mediated inactivation of lactonase activity is prevented by catalase (90%), oleic acid (73% at 0.01 mM) and dioleoylphosphatidylcholine (68% at 0.1 mM). Ascorbate/Fe2+ (0.5 mM/0.002 mM) system shows 20% inactivation

CdCl2

-

77.7% residual activity after 24 h in the presence of 0.02 mg/ml CdCl2

Cu2+

-

inhibits in a concentration-dependent manner. Cu2+ alone inhibits the lactonase activity by 30% at concentrations as low as 0.001 mM. Ascorbate/Cu2+ system is the most potent in inactivating the lactonase activity (by 90%). Cu2+ remarkably enhances the inactivation in the presence of ascorbate. Ascorbate/Cu2+ (0.5 mM/0.001 mM) system shows ca. 95% inactivation. Ascorbate/Cu2+-mediated inactivation of lactonase activity is prevented by catalase (90%), oleic acid (73% at 0.01 mM) and dioleoylphosphatidylcholine (68% at 0.1 mM)

D-penicillamine

-

32.4% residual activity after 24 h in the presence of 0.2 mg/ml D-penicillamine

diclofenac sodium

-

diclofenac sodium in 0.845 mM dose during 6-12 h of incubation results in a significant decline in the lactonase activity

749762

EDTA

Fe2+

-

ascorbate/Fe2+ (0.5 mM/0.002 mM) system shows 20% inactivation. Fe2+ alone shows no inhibition

high density lipoprotein

-

incubation of serum or high density lipoprotein from healthy subjects with very low density lipoprotein significantly decreases serum paraoxonase 1 lactonase or arylesterase activities by up to 11% or 24%, and HDL-associated paraoxonase 1 lactonase or arylesterase activities by up to 32% or 46%, respectively

-

Mg2+

nitrilotriacetic acid

-

PCMB

-

0.1 mM

PMSF

1 mM

sodium hypochlorite

-

at 1 mM and 10 mM causes approximately 18 and 34% decrease in lactonase activity, respectively

tenoxicam

-

tenoxicam in 0.74mM dose during 6 h of incubation results in a significant decline in the lactonase activity

749762

very low density lipoprotein

-

inhibits recombinant paraoxonase 1 lactonase or arylesterase activities by up to 20% or 42%, respectively

-

Zn2+

activity is strongly reduced when Ca2+ is removed from the purified enzyme and replaced by Zn2+

additional information

-

neither ascorbate alone nor Mn2+, Zn2+, Co2+ or 3-morpholinosydnoimine cause a significant loss of lactonase activity

-

apolipoprotein apoA-I

only apolipoprotein apoA-I is capable of stimulating the lactonase activity, while apoA-IV and apoA-II have almost no effect

664064

-

dilauroyl phosphatidylcholine

stimulates activity of enzyme variants Q192 and R192

phosphate

-

maintains activity, modulates oligomeric state

additional information

-

1.316

(R)-gamma-valerolactone

-

at pH 7.0 and 30°C

0.013 - 0.02

2-coumaranone

4.5

3-hydroxyoctanoate

-

0.27 - 1.83

5-(thiobutyl)butyrolactone

0.812

delta-nonalactone

pH 8.0

0.4 - 8.5

delta-valerolactone

11 entries

0.013 - 0.84

dihydrocoumarin

5.3 - 36.8

gamma-butyrolactone

6 entries

0.9 - 3.8

Gamma-caprolactone

5 entries

0.22

gamma-dodecanoic acid lactone

pH 8.0

0.3 - 0.7

gamma-dodecanoic lactone

0.58

gamma-heptanolide

pH 8.0

9 - 10.4

Gamma-hydroxyvalerate

0.39 - 1.54

gamma-nonalactone

0.39

gamma-nonanoic acid lactone

pH 8.0

1.3

Gamma-octalactone

-

2.8 - 3.5

gamma-thiobutyrolactone

0.6

gamma-undecanoic acid lactone

pH 8.0

0.6

gamma-undecanoiclactone

-

recombinant enzyme

3.3

gamma-valerolactone

-

21.2 - 23.5

homocysteine thiolactone

0.45 - 0.52

Homogentisic acid lactone

4.3

pantoyl lactone

pH 8.0

0.83

phenyl acetate

pH 8.0, 37°C

670788

36.621

(R)-gamma-valerolactone

-

at pH 7.0 and 30°C

39

4-methoxy phenyl acetate

pH 8.0

1.74 - 116

5-(thiobutyl)butyrolactone

48

delta-nonalactone

pH 8.0

0.5 - 632

delta-valerolactone

11 entries

152

dihydrocoumarin

pH 8.0

111 - 147.209

gamma-butyrolactone

2.27 - 44

Gamma-caprolactone

26.4

gamma-dodecanoic acid lactone

pH 8.0

34 - 101

gamma-dodecanoic lactone

34

gamma-heptanolide

pH 8.0

0.38 - 31

gamma-nonalactone

31

gamma-nonanoic acid lactone

pH 8.0

62

gamma-undecanoic acid lactone

pH 8.0

62

gamma-undecanoiclactone

-

recombinant enzyme

11.9

pantoyl lactone

pH 8.0

27.82

(R)-gamma-valerolactone

-

at pH 7.0 and 30°C

1.3 - 73.3

2-coumaranone

1.3 - 19.8

delta-valerolactone

4

gamma-butyrolactone

-

at pH 7.0 and 30°C

1.11 - 21.2

homocysteine thiolactone

0.0268

pH 8.0, 25°C, substrate: DL-3-oxo-hexanoyl-homoserine lactone, purified recombinant enzyme

0.0311

pH 8.0, 25°C, substrate: DL-heptanoyl-homoserine lactone, purified recombinant enzyme

0.4239

pH 8.0, 25°C, substrate: DL-tetradecanoyl-homoserine lactone, purified recombinant enzyme

0.4588

pH 8.0, 25°C, substrate: DL-dodecanoyl-homoserine lactone, purified recombinant enzyme

0.68

pH 8.0, 25°C, substrate: gamma-phenyl-gamma-butyrolactone, purified recombinant enzyme

1.83

pH 8.0, 25°C, substrate: 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid 1,5-lactone, purified recombinant enzyme

10.9

pH 8.0, 25°C, substrate: 2-coumaranone, purified recombinant enzyme

3.1

pH 8.0, 25°C, substrate: dihydrocoumarin, purified recombinant enzyme

0.0035

pH 8.0, 25°C, substrate: DL-tetradecanoyl-homoserine lactone, purified recombinant enzyme

0.0036

pH 8.0, 25°C, substrate: DL-heptanoyl-homoserine lactone, purified recombinant enzyme

0.0049

pH 8.0, 25°C, substrate: DL-heptanoyl-homoserine lactone, purified recombinant enzyme

0.011

pH 8.0, 25°C, substrate: spironolactone, purified recombinant enzyme

0.013

pH 8.0, 25°C, substrate: canrenone, purified recombinant enzyme

0.0167

pH 8.0, 25°C, substrate: DL-dodecanoyl-homoserine lactone, purified recombinant enzyme

0.0255

pH 8.0, 25°C, substrate: DL-tetradecanoyl-homoserine lactone, purified recombinant enzyme

0.0334

pH 8.0, 25°C, substrate: DL-3-oxo-hexanoyl-homoserine lactone, purified recombinant enzyme

0.0977

pH 8.0, 25°C, substrate: DL-dodecanoyl-homoserine lactone, purified recombinant enzyme

0.266

pH 8.0, 25°C, substrate: lovastatin, purified recombinant enzyme

0.81

pH 8.0, 25°C, substrate: gamma-butyrolactone, purified recombinant enzyme

11.1

pH 8.0, 25°C, substrate: delta-nonalactone, purified recombinant enzyme

11.4

pH 8.0, 25°C, substrate: gamma-phenyl-gamma-butyrolactone, purified recombinant enzyme

11.7

pH 8.0, 25°C, substrate: delta-hexalactone, purified recombinant enzyme

126.1

pH 8.0, 25°C, substrate: dihydrocoumarin, purified recombinant enzyme

127.6

pH 8.0, 25°C, substrate: gamma-undecanolactone, purified recombinant enzyme

129.9

pH 8.0, 25°C, substrate: dihydrocoumarin, purified recombinant enzyme

135.7

pH 8.0, 25°C, substrate: 2-coumaranone, purified recombinant enzyme

14.5

pH 8.0, 25°C, substrate: delta-valerolactone, purified recombinant enzyme

144.7

pH 8.0, 25°C, substrate: gamma-nonalactone, purified recombinant enzyme

150

pH 8.0, 25°C, substrate: delta-nonalactone, purified recombinant enzyme

154

pH 8.0, 25°C, substrate: delta-tetradecanolactone, purified recombinant enzyme

173.8

pH 8.0, 25°C, substrate: gamma-decanolactone, purified recombinant enzyme

183

pH 8.0, 25°C, substrate: alpha-angelicalactone, purified recombinant enzyme

20.7

pH 8.0, 25°C, substrate: alpha-angelicalactone, purified recombinant enzyme

212

-

22.7

pH 8.0, 25°C, substrate: delta-tetradecanolactone, purified recombinant enzyme

23.9

pH 8.0, 25°C, substrate: gamma-hexalactone, purified recombinant enzyme

25.6

pH 8.0, 25°C, substrate: gamma-octalactone, purified recombinant enzyme

251

pH 8.0, 25°C, substrate: delta-decanolactone, purified recombinant enzyme

27.5

pH 8.0, 25°C, substrate: 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid 1,5-lactone, purified recombinant enzyme

27.7

pH 8.0, 25°C, substrate: gamma-heptalactone, purified recombinant enzyme

287

pH 8.0, 25°C, substrate: delta-undecanolactone, purified recombinant enzyme

30.9

pH 8.0, 25°C, substrate: gamma-nonalactone, purified recombinant enzyme

32.1

pH 8.0, 25°C, substrate: gamma-butyrolactone, purified recombinant enzyme

329.5

pH 8.0, 25°C, substrate: homogentisic acid lactone, purified recombinant enzyme

40.7

pH 8.0, 25°C, substrate: 2-coumaranone, purified recombinant enzyme

44.3

pH 8.0, 25°C, substrate: delta-decanolactone, purified recombinant enzyme

45

pH 8.0, 25°C, substrate: gamma-valerolactone, purified recombinant enzyme

45.6

pH 8.0, 25°C, substrate: gamma-decanolactone, purified recombinant enzyme

51.7

pH 8.0, 25°C, substrate: gamma-hexalactone, purified recombinant enzyme

57.2

pH 8.0, 25°C, substrate: gamma-heptalactone, purified recombinant enzyme

6.2

pH 8.0, 25°C, substrate: gamma-valerolactone, purified recombinant enzyme

63

pH 8.0, 25°C, substrate: gamma-phenyl-gamma-butyrolactone, purified recombinant enzyme

671

pH 8.0, 25°C, substrate: delta-valerolactone, purified recombinant enzyme

69.2

pH 8.0, 25°C, substrate: gamma-octalactone, purified recombinant enzyme

71.4

pH 8.0, 25°C, substrate: gamma-undecanolactone, purified recombinant enzyme

72

pH 8.0, 25°C, substrate: delta-hexalactone, purified recombinant enzyme

75.4

pH 8.0, 25°C, substrate: 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid 1,5-lactone, purified recombinant enzyme

84.4

pH 8.0, 25°C, substrate: delta-undecanolactone, purified recombinant enzyme

additional information

new enzymatic tests are developed that detect total PON1 levels, irrespective of high-density lipoprotein status and R/Q polymorphism, as well as the degree of catalytic stimulation and increased stability that follows tight binding of PON1 to HDLapoA-I. The tests are based on measuring total PON1 levels with a fluorogenic phosphotriester, measuring the lipolactonase activity with a chromogenic lactone, and assaying the chelator-mediated inactivation rate of the enzyme. The latter two are affected by tight binding of high-density lipoprotein and thereby derive the levels of the serum PON1-HDL complex. The new tests are demonstrated with a group of healthy individuals and show that the levels of PON1-HDL vary by a factor of 12

681264

8

assay at

6

8

assay at

8.5

-

8.6

5 - 10

pH 5.0: about 55% of maximal activity, pH 10.0: about 35% of maximal activity

663985

25

assay at

25

32

-

37

assay at

15 - 37

-

15°C: about 65% of maximal activity, 37°C: about 90% of maximal activity

-

UniProt

-

the enzyme is expressed mainly in the liver

-

-

-

additional information

high density lipoprotein-associated enzyme

-

physiological function

the presence of a particular amino acid residue at position 192 differentially alters the effect of the H115W substitution, and the H115 residue is not always needed for the lactonase and arylesterase activities of the enzyme. The amino acid residues at position 192 and 115 act in conjunction in modulating the hydrolytic activities of the enzyme

Q15165 pBLAST

PON2_HUMAN

354

0

39381

Swiss-Prot

Show Sequence

-

17500

recombinant enzyme, nondenaturing PAGE

42000

3 * 42000, recombinant enzyme, SDS-PAGE

39000

2 * 39000, recombinant enzyme

40000

45000

-

x * 45000, SDS-PAGE

702421, 715735

91900

serum enzyme, nondenaturing PAGE

94900

recombinant enzyme, nondenaturing PAGE

95600

recombinant enzyme, nondenaturing PAGE

trimer

3 * 42000, recombinant enzyme, SDS-PAGE

?

dimer

glycoprotein

-

glycoprotein

C284A

no lactonase activity with either homogentisic acid lactone or undecanoic-delta-lactone

D183N

-

the mutant disfavors paraoxon binding due to its charged nature and possible electrostatic repulsion with the phosphate group of paraoxon

F222D

-

the mutation abolishes both esterase and PON activity of PON1

F222Y

-

the mutation abolishes the PON activity of PON1 but retains the esterase activity with a 1.5fold increase in KM for phenyl acetate

H115A

activity with dicoumarin is 366% compared to wild-type activity, activity with delta-valerolactone is 3% of wild-type activity, activity with gamma-nonalactone is 1% of wild-type activity

H115Q

activity with dicoumarin is 268% compared to wild-type activity, activity with delta-valerolactone is 4.96% of wild-type activity, activity with gamma-nonalactone is 1.2% of wild-type activity. kcat/Km for delta-valerolactone is 2.2% of wild-type value, kcat/Km for gamma-nonalactone is 0.3% of wild-type value, kcat/Km for gamma-caprolactone is 1.4% of wild-type value, kcat/Km for 5-(thiobutyl)butyrolactone is 1.1% of wild-type value. Mutant with reduced lactonase activity, exhibits reduced or no biological function in ex vivo assay

H115Q/H134Q

kcat/Km for 5-(thiobutyl)butyrolactone is 0.2% of wild-type value mutant with reduced lactonase activity, exhibits reduced or no biological function in ex vivo assay

H115W

H115W/R192K

kinetic parameters comparable to mutant H115W

H115W/R192Q

complete loss of activity

H134Q

activity with dicoumarin is 77% compared to wild-type activity, activity with delta-valerolactone is 13% of wild-type activity, activity with gamma-nonalactone is 22% of wild-type activity. kcat/Km for delta-valerolactone is 11% of wild-type value, kcat/Km for gamma-nonalactone is 8% of wild-type value, kcat/Km for gamma-caprolactone is 19% of wild-type value, kcat/Km for 5-(thiobutyl)butyrolactone is 6.5% of wild-type value. Mutant with reduced lactonase activity, exhibits reduced or no biological function in ex vivo assay

H184Q

activity with dicoumarin is 57% compared to wild-type activity, activity with delta-valerolactone is 44% of wild-type activity, activity with gamma-nonalactone is 44% of wild-type activity

H184T

activity with dicoumarin is 17% compared to wild-type activity, activity with delta-valerolactone is 35% of wild-type activity, activity with gamma-nonalactone is 39% of wild-type activity

H285Q

activity with dicoumarin is 22% compared to wild-type activity, activity with delta-valerolactone is 20% of wild-type activity, activity with gamma-nonalactone is 38% of wild-type activity

H285S

activity with dicoumarin is 13% compared to wild-type activity, activity with delta-valerolactone is 8% of wild-type activity, activity with gamma-nonalactone is 16% of wild-type activity

L55M

-

the mutant enzyme shows decreased lactonase activities compared to the wild type

L69G/S111T/H115W/H134R/R192K/F222S/T332S

mutant designed for expression in Escherichia coli in soluble and active form. Activity towards delta-valerolactone and homocysteinthiolactone is similar to wild-type, ativity towards N-oxododecanoyl-DL-homoserine lactone is 4fold increased

L69V

-

the mutant shows a 4-16fold increase in PON1 activity compared to the wild type enzyme

L69V/V369A

-

the mutant shows increased paraoxon binding affinity compared to the wild type enzyme

Q192R

R180T

-

the mutant retains a partial hydrolyzing activity against homocysteinethiolactone, whereas the delta-valerolactone-hydrolyzing activity is completely abolished

R192Q

-

the polymorphic residue R192Q interacts with the leaving group of paraoxon, suggesting it plays an important role in the proper positioning of this substrate in the active site

S193P

-

the mutation increases phosphotriesterase activity of PON1

V346A

-

the mutant shows a 4-16fold increase in PON1 activity compared to the wild type enzyme

additional information

the presence of a (His)6-tag at the N-terminus and at both the N- and C-termini decreases the enzymatic activity of the recombinant protein. The activity is unaffected by the presence of a (His)6-tag at its C-terminus

4.5 - 9

lactonase activity is quite stable

663985

90

-

4 min, complete loss of activity

94285

association of paraoxonase 1 with high-density lipoprotein stabilizes the enzyme

692732

Ca2+, 1 mM, stabilizes

-

4°C, 6 months, less than 15% loss of activity

4°C, 50 mM Tris buffer, 50 mM NaCl, 1 mM CaCl2, 0.1% tergitol, pH 8.0, 1 month

-

4°C, 6 months, less than 15% loss of activity

4°C, purified recombinant enzyme preparations typically lose about 20% of the arylesterase activity within the first month after purification, compared with less than 10% loss for the enzyme purified from serum. There is no further significant loss of the enzyme activity afterward, suggesting the existence of two pools in the purified enzyme, a labile one and a stable one

4°C, the enzyme activity is significantly lower after 48 h as well as after 1, 2 and 4 weeks storage when compared to enzyme activities assayed in fresh serum

-

-

-

ammonium sulfate precipitation, DEAE-Trisacryl M column chromatography, Sephacryl S300HR gel filtration, and Cibacron Blue 3GA gel filtration

-

715735

anion-exchange chromatography and concanavalin-A chromatography

692445

by different types of chromatographies

-

by pseudo-affinity chromatography and gel filtration

-

Ni-NTA column chromatography

-

Q-Sepharose column chromatography

-

wild-type-like rePON1-G2E6 and its various mutants are expressed as fusion proteins with thioredoxin and His6 tags

the recombinant enzyme is expressed in Trichoplusia ni High Five insect cells

-

-

expressed in baculovirus system in Hi5 insect cells

692445

expressed in Drosophila melanogaster

693354

expressed in Escherichia coli BL21(DE3) cells

-

expressed in Escherichia coli Origami B (DE3) cells

-

expression in Escherichia coli

expression of PON3 in Spodoptera frugiperda Sf9 cells using the baculovirus expression system

663985

the recombinant enzyme is expressed in Trichoplusia ni High Five insect cells

wild-type-like rePON1-G2E6 and its various mutants are expressed as fusion proteins with thioredoxin and His6 tags

enzyme activities and levels are higher in polycystic ovarian syndrome patients than in the control group

-

enzyme activities in fluorosis patients are considerably decreased up to 56.45% (mild), 61.5% (moderate) and 50% (severe) as compared to control group

-

750345

medicine

-

incubation of serum or high density lipoprotein from healthy subjects with very low density lipoprotein significantly decreases serum paraoxonase 1 lactonase or arylesterase activities by up to 11% or 24%, and HDL-associated paraoxonase 1 lactonase or arylesterase activities by up to 32% or 46%, respectively. Very low density lipoprotein also inhibits recombinant paraoxonase 1 lactonase or arylesterase activities by up to 20% or 42%, respectively. Bezafibrate therapy to three hypertriglyceridemic patients (400 mg/day, for one month) significantly decreased serum triglyceride concentration by 67%, and increased serum high density lipoproteincholesterol levels by 48%. Paraoxonase 1 arylesterase or paraoxonase activities in the patients' high density lipoprotein fractions after drug therapy are significantly increased by 86-88%, as compared to paraoxonase 1 activities before treatment. High density lipoprotein-paraoxonase 1 protein levels significantly increased after bezafibrate therapy

94285

Fishbein, W.N.; Bessman, S.P.

Purification and properties of an enzyme in human blood and rat liver microsomes catalyzing the formation and hydrolysis of gamma-lactones. I. Tissue localization, stoichiometry, specificity, distinction from esterase

J. Biol. Chem.

241

4835-4841

1966

Homo sapiens, Rattus norvegicus

4958984

Fishbein, W.N.; Bessman, S.P.

Purification and properties of an enzyme in human blood and rat liver microsomes catalyzing the formation and hydrolysis of gamma-lactones. II. Metal ion effects, kinetics, and equilibria

J. Biol. Chem.

241

4842-4847

1966

Homo sapiens, Rattus norvegicus

4958985

Billecke, S.; Draganov, D.; Counsell, R.; Stetson, P.; Watson, C.; Hsu, C.; La Du, B.N.

Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters

Drug Metab. Dispos.

28

1335-1342

2000

Homo sapiens (P27169)

11038162

663985

Lu, H.; Zhu, J.; Zang, Y.; Ze, Y.; Qin, J.

Cloning, high level expression of human paraoxonase-3 in Sf9 cells and pharmacological characterization of its product

Biochem. Pharmacol.

70

1019-1025

2005

Homo sapiens (Q15166)

16099434

664064

Gaidukov, L.; Tawfik, D.S.

High affinity, stability, and lactonase activity of serum paraoxonase PON1 anchored on HDL with ApoA-I

Biochemistry

44

11843-11854

2005

Homo sapiens (P27169)

16128586

Khersonsky, O.; Tawfik, D.S.

Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase

Biochemistry

44

6371-6382

2005

Homo sapiens (P27169)

15835926

Khersonsky, O.; Tawfik, D.S.

The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases

J. Biol. Chem.

281

7649-7656

2006

Homo sapiens (P27169), Oryctolagus cuniculus (Q9BGN0)

16407305

Draganov, D.I.; Teiber, J.F.; Speelman, A.; Osawa, Y.; Sunahara, R.; La Du, B.N.

Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities

J. Lipid Res.

46

1239-1247

2005

Homo sapiens (P27169), Homo sapiens (Q15165), Homo sapiens (Q15166)

15772423

670788

Lu, H.; Zhu, J.; Zang, Y.; Ze, Y.; Qin, J.

Cloning, purification, and refolding of human paraoxonase-3 expressed in Escherichia coli and its characterization

Protein Expr. Purif.

46

92-99

2006

Homo sapiens (Q15166)

16139510

681264

Gaidukov, L.; Tawfik, D.S.

The development of human sera tests for HDL-bound serum PON1 and its lipolactonase activity

J. Lipid Res.

48

1637-1646

2007

Homo sapiens (P27169)

17435182

Tavori, H.; Khatib, S.; Aviram, M.; Vaya, J.

Characterization of the PON1 active site using modeling simulation, in relation to PON1 lactonase activity

Bioorg. Med. Chem.

16

7504-7509

2008

Homo sapiens (P27169)

18572410

692445

Liu, Y.; Mackness, B.; Mackness, M.

Comparison of the ability of paraoxonases 1 and 3 to attenuate the in vitro oxidation of low-density lipoprotein and reduce macrophage oxidative stress

Free Radic. Biol. Med.

45

743-748

2008

Homo sapiens (Q15166)

18585453

692732

Rock, W.; Rosenblat, M.; Miller-Lotan, R.; Levy, A.P.; Elias, M.; Aviram, M.

Consumption of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities

J. Agric. Food Chem.

56

8704-8713

2008

Homo sapiens (P27169)

18759451

693354

Stoltz, D.A.; Ozer, E.A.; Taft, P.J.; Barry, M.; Liu, L.; Kiss, P.J.; Moninger, T.O.; Parsek, M.R.; Zabner, J.

Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1

J. Clin. Invest.

118

3123-3131

2008

Homo sapiens (P27169)

18704198

Hu, X.; Jiang, X.; Lenz, D.E.; Cerasoli, D.M.; Wallqvist, A.

In silico analyses of substrate interactions with human serum paraoxonase 1

Proteins

75

486-498

2009

Homo sapiens

18951406

Nguyen, S.D.; Hung, N.D.; Cheon-Ho, P.; Ree, K.M.; Dai-Eun, S.

Oxidative inactivation of lactonase activity of purified human paraoxonase 1 (PON1)

Biochim. Biophys. Acta

1790

155-160

2009

Homo sapiens

19103263

Renault, F.; Carus, T.; Clery-Barraud, C.; Elias, M.; Chabriere, E.; Masson, P.; Rochu, D.

Integrative analytical approach by capillary electrophoresis and kinetics under high pressure optimized for deciphering intrinsic and extrinsic cofactors that modulate activity and stability of human paraoxonase (PON1)

J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.

878

1346-1355

2010

Homo sapiens, synthetic construct

19945920

715735

Bayrak, A.; Bayrak, T.; Demirpence, E.; Kilinc, K.

Differential hydrolysis of homocysteine thiolactone by purified human serum (192)Q and (192)R PON1 isoenzymes

J. Chromatogr. B

879

49-55

2011

Homo sapiens

21123122

Bajaj, P.; Aggarwal, G.; Tripathy, R.K.; Pande, A.H.

Interplay between amino acid residues at positions 192 and 115 in modulating hydrolytic activities of human paraoxonase 1

Biochimie

105

202-210

2014

Homo sapiens (P27169)

25107406

Rosenblat, M.; Ward, S.; Volkova, N.; Hayek, T.; Aviram, M.

VLDL triglycerides inhibit HDL-associated paraoxonase 1 (PON1) activity: in vitro and in vivo studies

Biofactors

38

292-299

2012

Homo sapiens

22674772

Bajaj, P.; Tripathy, R.K.; Aggarwal, G.; Pande, A.H.

Characterization of human paraoxonase 1 variants suggest that His residues at 115 and 134 positions are not always needed for the lactonase/arylesterase activities of the enzyme

Protein Sci.

22

1799-1807

2013

Homo sapiens (P27169)

24123308

Tripathy, R.K.; Aggarwal, G.; Bajaj, P.; Kathuria, D.; Bharatam, P.V.; Pande, A.H.

Towards understanding the catalytic mechanism of human paraoxonase 1 experimental and in silico mutagenesis studies

Appl. Biochem. Biotechnol.

182

1642-1662

2017

Homo sapiens

28161867

749762

Solmaz Avcikurt, A.; Korkut, O.

Effect of certain non-steroidal anti-inflammatory drugs on the paraoxonase 2 (PON2) in human monocytic cell line U937

Arch. Physiol. Biochem.

124

378-382

2018

Homo sapiens

29199478

750345

Arulkumar, M.; Vijayan, R.; Penislusshiyan, S.; Sathishkumar, P.; Angayarkanni, J.; Palvannan, T.

Alteration of paraoxonase, arylesterase and lactonase activities in people around fluoride endemic area of Tamil Nadu, India

Clin. Chim. Acta

471

206-215

2017

Homo sapiens

28579140

Bizon, A.; Milnerowicz, H.

The effect of divalent metal chelators and cadmium on serum phosphotriesterase, lactonase and arylesterase activities of paraoxonase 1

Environ. Toxicol. Pharmacol.

58

77-83

2018

Homo sapiens

29306821

Zhang, Y.; Liu, H.; He, J.; Xu, K.; Bai, H.; Wang, Y.; Zhang, F.; Zhang, J.; Cheng, L.; Fan, P.

Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

Eur. J. Endocrinol.

172

391-402

2015

Homo sapiens

25575948

750511

Perla-Kajan, J.; Borowczyk, K.; Glowacki, R.; Nygard, O.; Jakubowski, H.

Paraoxonase 1 Q192R genotype and activity affect homocysteine thiolactone levels in humans

FASEB J.

32

6019

2018

Homo sapiens

29782204