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Information on EC 2.7.1.33 - pantothenate kinase and Organism(s) Staphylococcus aureus and UniProt Accession Q6G7I0

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Staphylococcus aureus
UNIPROT: Q6G7I0 not found.
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The taxonomic range for the selected organisms is: Staphylococcus aureus
The enzyme appears in selected viruses and cellular organisms
Synonyms
pank2, pantothenate kinase, pantothenate kinase 2, pank1, pank3, pank4, pank-iii, pfpank1, pantothenate kinase-2, type ii pantothenate kinase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
type II pantothenate kinase
-
coaW
A0A167Z3Z6
-
D-pantothenate kinase
-
-
-
-
hPanK
-
-
-
-
hPanK1
-
-
-
-
hPANK2
-
-
-
-
hPanK3
-
-
-
-
hPanK4
-
-
-
-
kinase, pantothenate (phosphorylating)
-
-
-
-
mPank
-
-
-
-
mPank1
-
-
-
-
mPanK3
-
-
-
-
PAK
-
-
-
-
pantothenic acid kinase
-
-
-
-
rPanK4
-
-
-
-
Rts protein
-
-
-
-
type III pantothenate kinase
A0A167Z3Z6
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + (R)-pantothenate = ADP + (R)-4'-phosphopantothenate
show the reaction diagram
bi bi mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
ATP:(R)-pantothenate 4'-phosphotransferase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9026-48-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + (R)-pantothenate
ADP + (R)-4'-phosphopantothenate
show the reaction diagram
ATP + (R)-pantothenate
ADP + (R)-4'-phosphopantothenate
show the reaction diagram
ATP + D-pantothenate
ADP + D-4'-phosphopantothenate
show the reaction diagram
-
-
-
-
?
ATP + N-heptylpantothenamide
ADP + N-heptylpantothenamide 4-phosphate
show the reaction diagram
ATP + N-pentylpantothenamide
ADP + N-pentylpantothenamide 4-phosphate
show the reaction diagram
-
-
-
-
?
ATP + pantothenate
ADP + (R)-4'-phosphopantothenate
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + (R)-pantothenate
ADP + (R)-4'-phosphopantothenate
show the reaction diagram
-
-
-
?
ATP + (R)-pantothenate
ADP + (R)-4'-phosphopantothenate
show the reaction diagram
ATP + N-heptylpantothenamide
ADP + N-heptylpantothenamide 4-phosphate
show the reaction diagram
-
substrate is converted to the inactive butyldethia-CoA analogue in the further downstream pathway leading to grwoth inhibition of the organism, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NH4+
induces a 5fold higher activation than either K+ or Rb+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-3-azido-4,4-dimethyl-dihydro-furan-2-one
-
-
(R)-4-(2,4-dihydroxy-3,3-dimethyl-butyrylamino)-butyric acid
-
78.7% inhibition at 0.1 mM, purified enzyme
(R)-4-(2-azido-4-hydroxy-3,3-dimethyl-butyrylamino)-butyric acid
-
-
(S)-4-(2,4-dihydroxy-3,3-dimethyl-butyrylamino)-butyric acid
-
54.6% inhibition at 0.1 mM, purified enzyme
(S)-trifluoro-methanesulfonic acid 4,4-dimethyl-2-oxo-tetrahydro-furan-3-yl-ester
-
-
2,4-dihydroxy-3,3-dimethyl N-(2-heptylcarbamoyl-ethyl)-butyramide
-
98.2% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-(2-isobutylcarbamoyl-ethyl)-butyramide
-
97.1% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-(2-pentylcarbamoyl-ethyl)-butyramide
-
98.8% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-(2-phenethylcarbamoyl-ethyl)-butyramide
-
89.5% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-(2-propylcarbamoylethyl)-butyramide
-
99.1% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-(2-[1-methyl-3-phenyl-propylcarbamoyl]-ethyl)-butyramide
-
86.4% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-(2-[2-(3,4-dimethoxy-phenyl)-ethylcarbamoyl]-ethyl)-butyramide
-
17.7% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-(2-[3,4,5-trimethoxy-benzylcarbamoyl]-ethyl)-butyramide
-
8.7% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(2,6,6-trimethylbicyclo[3.1.1]hept-3-ylcarbamoyl)-ethyl]-butyramide
-
76.6% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(2-ethoxy-ethylcarbamoyl)-ethyl]-butyramide
-
95.1% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(2-ethylsulfanylethylcarbamoyl)-ethyl]-butyramide
-
97.6% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(2-methylsulfanylethylcarbamoyl)-ethyl]-butyramide
-
96.5% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(2-morpholin-4-yl-ethylcarbamoyl)-ethyl]-butyramide
-
4.2% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(3,7-dimethylocta-2,6-dienylcarbamoyl)-ethyl]-butyramide
-
97.2% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(3-ethoxy-propylcarbamoyl)-ethyl]-butyramide
-
96.2% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(3-methylsulfanylpropylcarbamoyl)-ethyl]-butyramide
-
97.7% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[2-(4-methoxy-benzylcarbamoyl)-ethyl]-3,3-dimethyl-butyramide
-
53.9% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-3,3-dimethyl N-[3-(4-benzyl-piperazin-1-yl)-3-oxo-propyl]-butyramide
-
9.3% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-N-[2-(2-hydroxy-ethylcarbamoyl)-ethyl]-3,3-dimethyl-butyramide
-
72.2% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-N-[2-(2-methoxy-ethylcarbamoyl)-ethyl]-3,3-dimethyl-butyramide
-
90.1% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-N-[2-(3-hydroxy-propylcarbamoyl)-ethyl]-3,3-dimethyl-butyramide
-
i.e. pantothenol, 79.9% inhibition at 0.1 mM, purified enzyme
2,4-dihydroxy-N-[2-(3-methoxy-propylcarbamoyl)-ethyl]-3,3-dimethyl-butyramide
-
94.4% inhibition at 0.1 mM, purified enzyme
N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)pantothenamide
A0A167Z3Z6
-
N-(3-methoxyphenethyl)pantothenamide
A0A167Z3Z6
-
N-(5-methoxypentyl)pantothenamide
A0A167Z3Z6
-
N-(benzo[d][1,3]dioxol-5-ylmethyl)pantothenamide
A0A167Z3Z6
-
N-heptylpantothenamide
N-pentylpantothenamide
N-phenethylpantothenamide
A0A167Z3Z6
-
pantothenamide
A0A167Z3Z6
-
pantothenamide, N-substituted
-
IC50 about 0.0004-0.0016 mM
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
no feedback regulation by CoA or acetyl-CoA
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.023
(R)-pantothenate
-
pH 7.5, 37°C, recombinant enzyme
0.027 - 0.093
ATP
0.008
N-heptylpantothenamide
-
pH 7.5, 37°C, recombinant enzyme
0.003
N-pentylpantothenamide
-
pH 7.5, 37°C, recombinant enzyme
0.027 - 0.093
pantothenate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.7
(R)-pantothenate
-
pH 7.5, 37°C, recombinant enzyme
1.6
ATP
-
pH 7.5, 37°C, recombinant enzyme
0.425
N-heptylpantothenamide
-
pH 7.5, 37°C, recombinant enzyme
0.15
N-pentylpantothenamide
-
pH 7.5, 37°C, recombinant enzyme
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)pantothenamide
Staphylococcus aureus
A0A167Z3Z6
pH 7.6, 25°C
0.01
N-(3-methoxyphenethyl)pantothenamide
Staphylococcus aureus
A0A167Z3Z6
pH 7.6, 25°C
0.00013
N-(5-methoxypentyl)pantothenamide
Staphylococcus aureus
A0A167Z3Z6
pH 7.6, 25°C
0.00046
N-(benzo[d][1,3]dioxol-5-ylmethyl)pantothenamide
Staphylococcus aureus
A0A167Z3Z6
pH 7.6, 25°C
0.0048 - 0.018
N-heptylpantothenamide
0.0035 - 0.006
N-pentylpantothenamide
0.036
N-phenethylpantothenamide
Staphylococcus aureus
A0A167Z3Z6
pH 7.6, 25°C
0.0004 - 0.0016
pantothenamide, N-substituted
Staphylococcus aureus
-
IC50 about 0.0004-0.0016 mM
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6
A0A167Z3Z6
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
A0A167Z3Z6
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
A0A167Z3Z6
the potent antistaphylococcal activity of N-substituted pantothenamides (PanAms) exhibit inhibition of Staphylococcus aureus's atypical type II pantothenate kinase (SaPanKII), the first enzyme of coenzyme A biosynthesis. The mechanism of action follows from SaPanKII having a binding mode for PanAms that is distinct from those of other PanKs. Molecular interactions responsible for PanAm inhibitory activity, overview. The PanAms are phosphorylated by SaPanKII but remain bound at the active site, SaPanKII inhibition occurs via a delay in product release
metabolism
A0A167Z3Z6
CoA biosynthesis and salvage pathways, overview. The Staphylococcus aureus atypical type II pantothenate kinase (SaPanKII) is active in bothe pathways
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29000
-
2 * 29000, recombinant enzyme, SDS-PAGE
29100
-
x * 29100, recombinant enzyme, six-His-tagged
59000
-
recombinant enzyme, gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
x-ray crystallography
?
-
x * 29100, recombinant enzyme, six-His-tagged
dimer
-
2 * 29000, recombinant enzyme, SDS-PAGE
homodimer
A0A167Z3Z6
the subunit of the homodimers is composed of two domains (domains I and II) and the binding cap (residues 153-173), with a dimerization interface along helix alpha6
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with N-[2-(1,3-benzodioxol-5-yl)ethyl] pantothenamide, hanging drop vapor diffusion method, using 1.4 M sodium citrate, 0.1 M HEPES pH 7.5 and 5% (v/v) ethylene glycol
sitting drop vapour diffusion method using 28% (w/v) PEG 2 M and 0.1 M Bis-Tris (pH 6.5), at 18°C
purified recombinant enzyme SaPanKII in complex with inhibitors N-pentylpantothenamide, N-heptylpantothenamide, N-(5-methoxypentyl)pantothenamide, and N-(benzo[d][1,3]dioxol-5-ylmethyl)pantothenamide, sitting drop vapor diffusion method, 500 nl of 20-30 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 200 mM NaCl, and 10 mM dithiothreitol, and addition of 1.1% w/v cyclohexylethanoyl-N-hydroxyethylglucamide, ligand, and ATP, is mixed with 500 nl of well solution containing 25-35% PEG 4000, 0.2 M MgCl2, and 0.1 M Tris, pH 8.5, X-ray diffraction structure determination and analysis at 1.40-1.80 A resolution
A0A167Z3Z6
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D6A
reduced enzymatic activity
E70A
reduced enzymatic activity
K13A
reduced enzymatic activity
L11A
reduced enzymatic activity
L263P
reduced enzymatic activity
T10A
reduced enzymatic activity
Y137A
reduced enzymatic activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA resin column chromatography and Superdex 200 gel filtration
recombinant C-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, desalting gel filtration, anion exchange chromatography, gel filtration, and ultrafiltration
A0A167Z3Z6
recombinant enzyme, six-His-tagged
-
recombinant His6-tagged from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
gene coaA, expression of His6-tagged in Escherichia coli strain BL21(DE3)
-
gene coaW, recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)
A0A167Z3Z6
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Choudhry, A.E.; Mandichak, T.L.; Broskey, J.P.; Egolf, R.W.; Kinsland, C.; Begley, T.P.; Seefeld, M.A.; Ku, T.W.; Brown, J.R.; Zalacain, M.; Ratnam, K.
Inhibitors of pantothenate kinase: novel antibiotics for staphylococcal infections
Antimicrob. Agents Chemother.
47
2051-2055
2003
Staphylococcus aureus
Manually annotated by BRENDA team
Virga, K.G.; Zhang, Y.M.; Leonardi, R.; Ivey, R.A.; Hevener, K.; Park, H.W.; Jackowski, S.; Rock, C.O.; Lee, R.E.
Structure-activity relationships and enzyme inhibition of pantothenamide-type pantothenate kinase inhibitors
Bioorg. Med. Chem.
14
1007-1020
2006
Aspergillus nidulans, Escherichia coli, Mus musculus, Staphylococcus aureus
Manually annotated by BRENDA team
Leonardi, R.; Chohnan, S.; Zhang, Y.M.; Virga, K.G.; Lee, R.E.; Rock, C.O.; Jackowski, S.
A pantothenate kinase from Staphylococcus aureus refractory to feedback regulation by coenzyme A
J. Biol. Chem.
280
3314-3322
2005
Staphylococcus aureus, Staphylococcus aureus RN4220
Manually annotated by BRENDA team
Hong, B.S.; Yun, M.K.; Zhang, Y.M.; Chohnan, S.; Rock, C.O.; White, S.W.; Jackowski, S.; Park, H.W.; Leonardi, R.
Prokaryotic type II and type III pantothenate kinases: The same monomer fold creates dimers with distinct catalytic properties
Structure
14
1251-1261
2006
Staphylococcus aureus (Q6G7I0), Pseudomonas aeruginosa (Q9HWC1)
Manually annotated by BRENDA team
Spry, C.; Kirk, K.; Saliba, K.J.
Coenzyme A biosynthesis: an antimicrobial drug target
FEMS Microbiol. Rev.
32
56-106
2008
Escherichia coli, Staphylococcus aureus, Mycobacterium tuberculosis
Manually annotated by BRENDA team
Hughes, S.J.; Antoshchenko, T.; Kim, K.P.; Smil, D.; Park, H.W.
Structural characterization of a new N-substituted pantothenamide bound to pantothenate kinases from Klebsiella pneumoniae and Staphylococcus aureus
Proteins
82
1542-1548
2014
Klebsiella pneumoniae (B5XYG3), Klebsiella pneumoniae, Staphylococcus aureus (Q6G7I0), Staphylococcus aureus, Staphylococcus aureus MSSA476 (Q6G7I0), Klebsiella pneumoniae 342 (B5XYG3)
Manually annotated by BRENDA team
Hughes, S.J.; Barnard, L.; Mottaghi, K.; Tempel, W.; Antoshchenko, T.; Hong, B.S.; Allali-Hassani, A.; Smil, D.; Vedadi, M.; Strauss, E.; Park, H.W.
Discovery of potent pantothenamide inhibitors of Staphylococcus aureus pantothenate kinase through a minimal SAR study inhibition is due to trapping of the product
ACS Infect. Dis.
2
627-641
2016
Staphylococcus aureus (A0A167Z3Z6), Staphylococcus aureus, Staphylococcus aureus RN4220 (A0A167Z3Z6)
Manually annotated by BRENDA team