BRENDA - Enzyme Database show

Modulation of pantothenate kinase 3 activity by small molecules that interact with the substrate/allosteric regulatory domain

Leonardi, R.; Zhang, Y.M.; Yun, M.K.; Zhou, R.; Zeng, F.Y.; Lin, W.; Cui, J.; Chen, T.; Rock, C.O.; White, S.W.; Jackowski, S.; Chem. Biol. 17, 892-902 (2010)

Data extracted from this reference:

Activating Compound
EC Number
Activating Compound
Commentary
Organism
Structure
2.7.1.33
cholesterol
about 125% activity at 0.1 mM
Homo sapiens
2.7.1.33
glyburide
; isoform PanK1b is activated by glyburide
Homo sapiens
2.7.1.33
additional information
isoform PanK3 is not activated by 1,4-naphthoquinone and phenylmercuric acid
Homo sapiens
2.7.1.33
O-oleoylcarnitine
140% activation at 0.1 mM
Homo sapiens
2.7.1.33
O-palmitoylcarnitine
120% activation at 0.1 mM
Homo sapiens
2.7.1.33
oleoylethanolamide
120% activation at 0.1 mM
Homo sapiens
2.7.1.33
tamoxifen
140% activation at 0.1 mM
Homo sapiens
Engineering
EC Number
Amino acid exchange
Commentary
Organism
2.7.1.33
A267F
catalytically inactive
Homo sapiens
2.7.1.33
A269F
catalytically inactive
Homo sapiens
2.7.1.33
R207A
catalytically inactive
Homo sapiens
2.7.1.33
S195V
the mutant is insensitive to acetyl-CoA and has a KM defect for pantothenate
Homo sapiens
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
2.7.1.33
1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea dihydrobromide
-
Homo sapiens
2.7.1.33
acetyl-CoA
complete inhibition of isoform PanK3 at 0.008 mM
Homo sapiens
2.7.1.33
ADP
competitive inhibitor of isoform PanK3 with respect to ATP1 and a mixed-type inhibitor with respect to pantothenate
Homo sapiens
2.7.1.33
chloranil
-
Homo sapiens
2.7.1.33
dehydroisoandrosterone
about 30% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Dehydroisoandrosterone sulfate
; about 8% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
ephedrine hydrochloride
-
Homo sapiens
2.7.1.33
estradiol
about 80% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Estradiol sulfate
about 90% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Estrone sulfate
about 50% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Fusidic acid
-
Homo sapiens
2.7.1.33
glipizide
-
Homo sapiens
2.7.1.33
glyburide
-
Homo sapiens
2.7.1.33
GW5074
-
Homo sapiens
2.7.1.33
Hexachlorophene
-
Homo sapiens
2.7.1.33
MCC-555
MCC-555 inhibits all three isoforms with a rank order of PanK3 > PanK2 > PanK1b; MCC-555 inhibits all three isoforms with a rank order of PanK3 > PanK2 > PanK1b
Homo sapiens
2.7.1.33
additional information
isoform PanK3 is not inhibited by estrone
Homo sapiens
2.7.1.33
pioglitazone hydrochloride
-
Homo sapiens
2.7.1.33
pregnenolone sulfate
; about 10% residual activity at 0.1 mM (isoform PanK3); about 92% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Psi-rhodomyrtoxin
-
Homo sapiens
2.7.1.33
Reactive blue 2
-
Homo sapiens
2.7.1.33
Ro 41-0960
-
Homo sapiens
2.7.1.33
rosiglitazone
-
Homo sapiens
2.7.1.33
tamoxifen
-
Homo sapiens
2.7.1.33
tolfenamic acid
-
Homo sapiens
2.7.1.33
tyrphostin AG 528
-
Homo sapiens
2.7.1.33
tyrphostin AG 808
-
Homo sapiens
2.7.1.33
WIN 62577
-
Homo sapiens
KM Value [mM]
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
2.7.1.33
0.014
-
(R)-pantothenate
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
2.7.1.33
0.311
-
ATP
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.7.1.33
Homo sapiens
-
-
-
2.7.1.33
Homo sapiens
Q9H999
isoform PanK3
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
2.7.1.33
HepG2/C3A cell
;
Homo sapiens
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.7.1.33
ATP + (R)-pantothenate
-
722018
Homo sapiens
ADP + (R)-4'-phosphopantothenate
-
-
-
?
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.7.1.33
0.0001
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Fusidic acid
2.7.1.33
0.0004
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea dihydrobromide
2.7.1.33
0.0007
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
WIN 62577
2.7.1.33
0.001
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
pioglitazone hydrochloride
2.7.1.33
0.0013
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Reactive blue 2
2.7.1.33
0.0016
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
ephedrine hydrochloride
2.7.1.33
0.0016
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Psi-rhodomyrtoxin
2.7.1.33
0.0017
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
rosiglitazone
2.7.1.33
0.0025
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
pregnenolone sulfate
2.7.1.33
0.003
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
tyrphostin AG 528
2.7.1.33
0.0035
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Dehydroisoandrosterone sulfate
2.7.1.33
0.0039
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Ro 41-0960
2.7.1.33
0.0052
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
glipizide
2.7.1.33
0.0059
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
chloranil
2.7.1.33
0.0068
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
glyburide
2.7.1.33
0.0088
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Hexachlorophene
2.7.1.33
0.009
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
tyrphostin AG 808
2.7.1.33
0.0092
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
GW5074
2.7.1.33
0.0092
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
tolfenamic acid
Activating Compound (protein specific)
EC Number
Activating Compound
Commentary
Organism
Structure
2.7.1.33
cholesterol
about 125% activity at 0.1 mM
Homo sapiens
2.7.1.33
glyburide
isoform PanK1b is activated by glyburide
Homo sapiens
2.7.1.33
glyburide
-
Homo sapiens
2.7.1.33
additional information
isoform PanK3 is not activated by 1,4-naphthoquinone and phenylmercuric acid
Homo sapiens
2.7.1.33
O-oleoylcarnitine
140% activation at 0.1 mM
Homo sapiens
2.7.1.33
O-palmitoylcarnitine
120% activation at 0.1 mM
Homo sapiens
2.7.1.33
oleoylethanolamide
120% activation at 0.1 mM
Homo sapiens
2.7.1.33
tamoxifen
140% activation at 0.1 mM
Homo sapiens
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
2.7.1.33
A267F
catalytically inactive
Homo sapiens
2.7.1.33
A269F
catalytically inactive
Homo sapiens
2.7.1.33
R207A
catalytically inactive
Homo sapiens
2.7.1.33
S195V
the mutant is insensitive to acetyl-CoA and has a KM defect for pantothenate
Homo sapiens
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.7.1.33
0.0001
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Fusidic acid
2.7.1.33
0.0004
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea dihydrobromide
2.7.1.33
0.0007
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
WIN 62577
2.7.1.33
0.001
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
pioglitazone hydrochloride
2.7.1.33
0.0013
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Reactive blue 2
2.7.1.33
0.0016
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
ephedrine hydrochloride
2.7.1.33
0.0016
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Psi-rhodomyrtoxin
2.7.1.33
0.0017
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
rosiglitazone
2.7.1.33
0.0025
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
pregnenolone sulfate
2.7.1.33
0.003
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
tyrphostin AG 528
2.7.1.33
0.0035
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Dehydroisoandrosterone sulfate
2.7.1.33
0.0039
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Ro 41-0960
2.7.1.33
0.0052
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
glipizide
2.7.1.33
0.0059
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
chloranil
2.7.1.33
0.0068
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
glyburide
2.7.1.33
0.0088
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Hexachlorophene
2.7.1.33
0.009
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
tyrphostin AG 808
2.7.1.33
0.0092
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
GW5074
2.7.1.33
0.0092
-
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
tolfenamic acid
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
2.7.1.33
1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea dihydrobromide
-
Homo sapiens
2.7.1.33
acetyl-CoA
complete inhibition of isoform PanK3 at 0.008 mM
Homo sapiens
2.7.1.33
ADP
competitive inhibitor of isoform PanK3 with respect to ATP1 and a mixed-type inhibitor with respect to pantothenate
Homo sapiens
2.7.1.33
chloranil
-
Homo sapiens
2.7.1.33
dehydroisoandrosterone
about 30% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Dehydroisoandrosterone sulfate
; about 8% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
ephedrine hydrochloride
-
Homo sapiens
2.7.1.33
estradiol
about 80% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Estradiol sulfate
about 90% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Estrone sulfate
about 50% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Fusidic acid
-
Homo sapiens
2.7.1.33
glipizide
-
Homo sapiens
2.7.1.33
glyburide
-
Homo sapiens
2.7.1.33
GW5074
-
Homo sapiens
2.7.1.33
Hexachlorophene
-
Homo sapiens
2.7.1.33
MCC-555
MCC-555 inhibits all three isoforms with a rank order of PanK3 > PanK2 > PanK1b
Homo sapiens
2.7.1.33
additional information
isoform PanK3 is not inhibited by estrone
Homo sapiens
2.7.1.33
pioglitazone hydrochloride
-
Homo sapiens
2.7.1.33
pregnenolone sulfate
; about 10% residual activity at 0.1 mM (isoform PanK3); about 92% residual activity at 0.1 mM (isoform PanK3)
Homo sapiens
2.7.1.33
Psi-rhodomyrtoxin
-
Homo sapiens
2.7.1.33
Reactive blue 2
-
Homo sapiens
2.7.1.33
Ro 41-0960
-
Homo sapiens
2.7.1.33
rosiglitazone
-
Homo sapiens
2.7.1.33
tamoxifen
-
Homo sapiens
2.7.1.33
tolfenamic acid
-
Homo sapiens
2.7.1.33
tyrphostin AG 528
-
Homo sapiens
2.7.1.33
tyrphostin AG 808
-
Homo sapiens
2.7.1.33
WIN 62577
-
Homo sapiens
KM Value [mM] (protein specific)
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
2.7.1.33
0.014
-
(R)-pantothenate
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
2.7.1.33
0.311
-
ATP
isoform PanK3, at pH 7.5 and 37°C
Homo sapiens
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
2.7.1.33
HepG2/C3A cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.7.1.33
ATP + (R)-pantothenate
-
722018
Homo sapiens
ADP + (R)-4'-phosphopantothenate
-
-
-
?
General Information
EC Number
General Information
Commentary
Organism
2.7.1.33
metabolism
pantothenate kinase catalyzes the rate-controlling step in coenzyme A biosynthesis; pantothenate kinase catalyzes the rate-controlling step in coenzyme A biosynthesis
Homo sapiens
General Information (protein specific)
EC Number
General Information
Commentary
Organism
2.7.1.33
metabolism
pantothenate kinase catalyzes the rate-controlling step in coenzyme A biosynthesis
Homo sapiens