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Literature summary extracted from

  • Nurkanto, A.; Jeelani, G.; Yamamoto, T.; Naito, Y.; Hishiki, T.; Mori, M.; Suematsu, M.; Shiomi, K.; Hashimoto, T.; Nozaki, T.
    Characterization and validation of Entamoeba histolytica pantothenate kinase as a novel anti-amebic drug target (2018), Int. J. Parasitol. Drugs Drug Resist., 8, 125-136 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.7.1.33 drug development since Entamoeba histolytica PanK (EhPanK) is physiologically important and sufficiently divergent from its human orthologs, this enzyme represents an attractive target for the development of novel anti-amebic chemotherapies Entamoeba histolytica

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.33 gene EHI_183060, phylogenetic analysis, quantitative real-time PCR enzyme expression analysis, recombinant expression of Myc-tagged enzyme in Entamoeba histolytica strain HM-1:IMSS cl6, recombinant expression of His-tagged enzyme from pCOLD1-EhPanK in Escherichia coli strain BL21(DE3) cells Entamoeba histolytica

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.33 additional information epigenetic gene silencing of PanK resulting in a significant reduction of PanK activity, intracellular CoA concentrations, and growth retardation in vitro, reinforcing the importance of this gene in Entamoeba histolytica. In Pank-silenced cells, the genes encoding other enzymes involved in CoA biosynthesis are upregulated 1.2, 2.1, 3.0, and 5.2 fold for PPCS-PPCDC, PPAT, DPCK1, and DPCK2, respectively. Growth kinetic analysis Entamoeba histolytica

General Stability

EC Number General Stability Organism
2.7.1.33 enzyme EhPanK is robust Entamoeba histolytica

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.1.33 acetyl-CoA mixed-type inhibition versus pantothenate and ATP Entamoeba histolytica
2.7.1.33 cephaloridine
-
Entamoeba histolytica
2.7.1.33 CoA competitive versus ATP, uncompetitive versus pantothenate Entamoeba histolytica
2.7.1.33 echinomycin
-
Entamoeba histolytica
2.7.1.33 erythromycin A
-
Entamoeba histolytica
2.7.1.33 fluorescamine
-
Entamoeba histolytica
2.7.1.33 gardimycin
-
Entamoeba histolytica
2.7.1.33 hygromycin A
-
Entamoeba histolytica
2.7.1.33 kasugamycin
-
Entamoeba histolytica
2.7.1.33 malonyl CoA competitive versus ATP, uncompetitive versus pantothenate Entamoeba histolytica
2.7.1.33 additional information inhibitor library screening and evaluation of cytotoxicity against human fibroblast MRC-5 cells. IC50 values for cytotoxicity against Entamoeba trophozoites and human MRC-5 cells, overview Entamoeba histolytica
2.7.1.33 neomycin
-
Entamoeba histolytica
2.7.1.33 O-methylnanaomycin A
-
Entamoeba histolytica
2.7.1.33 rosamycin
-
Entamoeba histolytica
2.7.1.33 streptomycin
-
Entamoeba histolytica
2.7.1.33 teicoplanin
-
Entamoeba histolytica
2.7.1.33 tirandamycin A
-
Entamoeba histolytica
2.7.1.33 trichostatin A
-
Entamoeba histolytica

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.1.33 additional information
-
additional information Michaelis-Menten kinetics. EhPanK exhibits hyperbolic saturation kinetics when assayed over the substrate range of 0.004-0.256 mM for pantothenate in the presence of 0.025-0.10 mM ATP and 0.001-0.10 mM ATP in the presence of 0.008-0.128 mM pantothenate Entamoeba histolytica
2.7.1.33 0.0414
-
ATP pH 6.0, 37°C, recombinant enzyme Entamoeba histolytica
2.7.1.33 0.0532
-
(R)-pantothenate pH 6.0, 37°C, recombinant enzyme Entamoeba histolytica

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.1.33 cytosol
-
Entamoeba histolytica 5829
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.33 Ca2+ results in 17.0% activity compard to Mg2+ Entamoeba histolytica
2.7.1.33 Co2+ results in 74.2% activity compard to Mg2+ Entamoeba histolytica
2.7.1.33 Cu2+ results in 84.3% activity compard to Mg2+ Entamoeba histolytica
2.7.1.33 Fe2+ results in 72.8% activity compard to Mg2+ Entamoeba histolytica
2.7.1.33 Li+ results in 34.5% activity compard to Mg2+ Entamoeba histolytica
2.7.1.33 Mg2+ reuqired Entamoeba histolytica
2.7.1.33 Mg2+ best cation Entamoeba histolytica
2.7.1.33 Mn2+ results in 83.2% activity compard to Mg2+ Entamoeba histolytica
2.7.1.33 additional information EhPanK shows an absolute requirement for a free bivalent metal cofactor, with Mg2+ as the preferred cation. No activity with Ni2+, Na+, and K+ Entamoeba histolytica
2.7.1.33 Zn2+ results in 3.9% activity compard to Mg2+ Entamoeba histolytica

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.33 ATP + (R)-pantothenate Entamoeba histolytica
-
ADP + (R)-4'-phosphopantothenate
-
?
2.7.1.33 CTP + (R)-pantothenate Entamoeba histolytica
-
CDP + (R)-4'-phosphopantothenate
-
?
2.7.1.33 dATP + (R)-pantothenate Entamoeba histolytica
-
dADP + (R)-4'-phosphopantothenate
-
?
2.7.1.33 GTP + (R)-pantothenate Entamoeba histolytica
-
GDP + (R)-4'-phosphopantothenate
-
?
2.7.1.33 polyphosphate(n) + (R)-pantothenate Entamoeba histolytica
-
polyphosphate(n-1) + (R)-4'-phosphopantothenate
-
?
2.7.1.33 UTP + (R)-pantothenate Entamoeba histolytica
-
UDP + (R)-4'-phosphopantothenate
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.33 Entamoeba histolytica B1N2P3
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.1.33 recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) cells by nickel affinity chromatography Entamoeba histolytica

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.33 trophozoite
-
Entamoeba histolytica
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.33 ATP + (R)-pantothenate
-
Entamoeba histolytica ADP + (R)-4'-phosphopantothenate
-
?
2.7.1.33 CTP + (R)-pantothenate
-
Entamoeba histolytica CDP + (R)-4'-phosphopantothenate
-
?
2.7.1.33 dATP + (R)-pantothenate
-
Entamoeba histolytica dADP + (R)-4'-phosphopantothenate
-
?
2.7.1.33 GTP + (R)-pantothenate
-
Entamoeba histolytica GDP + (R)-4'-phosphopantothenate
-
?
2.7.1.33 additional information EhPanK utilizes various nucleoside triphosphates, ATP, CTP, GTP, UTP, dATP, and polyphosphates, as well as deoxynucleotides as phosphoryl donors, with ATP being the best phosphate donor Entamoeba histolytica ?
-
-
2.7.1.33 polyphosphate(n) + (R)-pantothenate
-
Entamoeba histolytica polyphosphate(n-1) + (R)-4'-phosphopantothenate
-
?
2.7.1.33 UTP + (R)-pantothenate
-
Entamoeba histolytica UDP + (R)-4'-phosphopantothenate
-
?

Synonyms

EC Number Synonyms Comment Organism
2.7.1.33 EhPAnK
-
Entamoeba histolytica
2.7.1.33 PanK
-
Entamoeba histolytica
2.7.1.33 pantothenate kinase 1
-
Entamoeba histolytica

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.1.33 37
-
-
Entamoeba histolytica

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.1.33 6
-
enzyme EhPanK is catalytically active in broad pH range Entamoeba histolytica

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7.1.33 0.0263
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica teicoplanin
2.7.1.33 0.0492
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica gardimycin
2.7.1.33 0.0778
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica echinomycin
2.7.1.33 0.1313
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica erythromycin A
2.7.1.33 0.1472
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica neomycin
2.7.1.33 0.1554
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica streptomycin
2.7.1.33 0.1657
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica rosamycin
2.7.1.33 0.1937
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica hygromycin A
2.7.1.33 0.2288
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica tirandamycin A
2.7.1.33 0.2299
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica cephaloridine
2.7.1.33 0.2541
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica kasugamycin
2.7.1.33 0.2838
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica O-methylnanaomycin A
2.7.1.33 0.3099
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica trichostatin A
2.7.1.33 0.3464
-
recombinant enzyme, pH 6.0, 37°C Entamoeba histolytica fluorescamine

General Information

EC Number General Information Comment Organism
2.7.1.33 malfunction epigenetic gene silencing of PanK resulting in a significant reduction of PanK activity, intracellular CoA concentrations, and growth retardation in vitro, reinforcing the importance of this gene in Entamoeba histolytica Entamoeba histolytica
2.7.1.33 metabolism four key enzymes are involved in the CoA pathway: pantothenate kinase (PanK, EC 2.7.1.33), bifunctional phosphopantothenate-cysteine ligase/decarboxylase (PPCS-PPCDC), phosphopantetheine adenylyltransferase (PPAT) and dephospho-CoA kinase (DPCK) Entamoeba histolytica