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Literature summary for 2.7.1.32 extracted from

  • Zimmerman, T.; Chasten, V.; Lacal, J.C.; Ibrahim, S.A.
    Identification and validation of novel and more effective choline kinase inhibitors against Streptococcus pneumoniae (2020), Sci. Rep., 10, 15418 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene licA, recombinant expression of enzyme sChoK in Escherichia coli strain BL21(DE3) Streptococcus pneumoniae

Inhibitors

Inhibitors Comment Organism Structure
1,1'-[butane-1,4-diylbis[(4,1-phenylene)methylene]]bis[4-(dimethylamino)pyridin-1-ium] MN58b, mixed inhibition type with both choline and ATP Streptococcus pneumoniae
1,1'-[[1,1'-biphenyl]-4,4'-diylbis(methylene)]bis[4-[(4-chlorophenyl)(methyl)amino]quinolin-1-ium] RSM-932A, mixed inhibition type with choline, non-competitive with ATP Streptococcus pneumoniae
hemicholinium-3 HC-3, MIC is 5.4 mM Streptococcus pneumoniae
additional information docking of MN58b and RSM-932A onto sChoK, overview. MN58b and RSM-932A fit into the active site of sChoK in a differential manner. In enzymatic assays with Streptoccocus pneumoniae extracts MN58b is still an inhibitor, while RSM-932A becomes an agonist Streptococcus pneumoniae

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information steady-state kinetics Streptococcus pneumoniae
0.13
-
choline recombinant enzyme, pH 8.0, 25°C Streptococcus pneumoniae

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Streptococcus pneumoniae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + choline Streptococcus pneumoniae
-
ADP + phosphocholine
-
?
ATP + choline Streptococcus pneumoniae ATCC BAA-255
-
ADP + phosphocholine
-
?

Organism

Organism UniProt Comment Textmining
Streptococcus pneumoniae Q8DPI4
-
-
Streptococcus pneumoniae ATCC BAA-255 Q8DPI4
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme sChoK from Escherichia coli strain BL21(DE3) Streptococcus pneumoniae

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + choline
-
Streptococcus pneumoniae ADP + phosphocholine
-
?
ATP + choline
-
Streptococcus pneumoniae ATCC BAA-255 ADP + phosphocholine
-
?

Synonyms

Synonyms Comment Organism
chbA
-
Streptococcus pneumoniae
ChoK
-
Streptococcus pneumoniae
LicA
-
Streptococcus pneumoniae
sChoK
-
Streptococcus pneumoniae

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Streptococcus pneumoniae

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.14
-
choline recombinant enzyme, pH 8.0, 25°C Streptococcus pneumoniae

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Streptococcus pneumoniae

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetics and MIC values Streptococcus pneumoniae
0.0106
-
1,1'-[[1,1'-biphenyl]-4,4'-diylbis(methylene)]bis[4-[(4-chlorophenyl)(methyl)amino]quinolin-1-ium] recombinant enzyme, pH 8.0, 25°C, versus choline Streptococcus pneumoniae
0.0358
-
1,1'-[[1,1'-biphenyl]-4,4'-diylbis(methylene)]bis[4-[(4-chlorophenyl)(methyl)amino]quinolin-1-ium] recombinant enzyme, pH 8.0, 25°C, versus ATP Streptococcus pneumoniae
0.124
-
1,1'-[butane-1,4-diylbis[(4,1-phenylene)methylene]]bis[4-(dimethylamino)pyridin-1-ium] recombinant enzyme, pH 8.0, 25°C, versus choline Streptococcus pneumoniae
0.182
-
1,1'-[butane-1,4-diylbis[(4,1-phenylene)methylene]]bis[4-(dimethylamino)pyridin-1-ium] recombinant enzyme, pH 8.0, 25°C, versus ATP Streptococcus pneumoniae

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7
-
recombinant enzyme, pH 8.0, 25°C Streptococcus pneumoniae hemicholinium-3

General Information

General Information Comment Organism
malfunction choline kinase inhibitor MN58b sensitizes Streptococcus pneumoniae cells to autolysis while inhibitor RSM-932A does not. MN58b and RSM-932A do not provoke or prevent autolysis. Effect of the drugs on LTA production, overview. MN58b but not RSM-932A causes deformation of the Streptococcus pneumoniae cell wall Streptococcus pneumoniae
metabolism the sChoK enzyme is an element of the pathway that mediates the decoration of teichoic acids with PCho via the intermediary CDP-choline Streptococcus pneumoniae
physiological function the choline kinase of S. pneumoniae (sChoK) is an essential enzyme. Choline kinase (ChoK) phosphorylates choline into phosphocholine. Phosphocholine is important because it a precursor molecule that is utilized in the production of two types of teichoic acids, lipoteichoic acid (LTA) and cell wall teichoic acid (CTA). sChoK plays a role in the growth and pathogenesis for humans of Gram-positive bacterium Streptococcus pneumoniae. In Streptococcus pneumoniae, both acids consist of the same types of polysaccharides but LTA is attached to a lipid and embedded in the cell membrane, and CTA is attached to the peptidoglycan molecules in the cell wall. LTA is an important virulence factor and LTA production has been validated as a drug target Streptococcus pneumoniae

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
24.15
-
choline recombinant enzyme, pH 8.0, 25°C Streptococcus pneumoniae