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Literature summary for 2.7.1.32 extracted from

  • Zimmerman, T.; Lacal, J.C.; Ibrahim, S.A.
    Choline kinase emerges as a promising drug target in Gram-positive bacteria (2019), Front. Microbiol., 6, 2146 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.1.32

Cloned(Commentary)

Cloned (Comment) Organism
gene licA, sequence comparison of Streptococcus pneumoniae and human enzymes, overview Streptococcus pneumoniae

Inhibitors

Inhibitors Comment Organism Structure
hemicholinium-3 HC-3, HC-3 competes with the Cho substrate by directly displacing it from the active site of hChoK. Hemocholinium-3 blocks cell division, reduces LTA production, distorts the cell wall, and inhibits sChoK activity Streptococcus pneumoniae
MN58b dysregulates the production of LTA, distorts the cell wall, and affects cell sensitivity to deoxycholate induced autolysis Streptococcus pneumoniae
additional information repurposing of drugs known to inhibit the human isoform of ChoK (hChoK), is a promising strategy for blocking the growth of Streptococcus pneumoniae cells and inhibiting the activity of the Streptococcus pneumoniae isoform of ChoK (sChok), with downstream physiological effects on the cell wall Streptococcus pneumoniae
RSM-932A dysregulates the production of LTA, distorts the cell wall, and affects cell sensitivity to deoxycholate induced autolysis Streptococcus pneumoniae

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Streptococcus pneumoniae
Mg2+ required Haemophilus influenzae

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 Haemophilus influenzae
-
 ADP + phosphocholine
-
 ?
ATP + choline Haemophilus influenzae R6
-
 ADP + phosphocholine
-
 ?
ATP + choline Haemophilus influenzae ATCC BAA-255
-
 ADP + phosphocholine
-
 ?
ATP + choline Streptococcus pneumoniae ATCC BAA-255
-
 ADP + phosphocholine
-
 ?

Organism

Organism UniProt Comment Textmining
Haemophilus influenzae P14181
-
-
Haemophilus influenzae ATCC BAA-255 P14181
-
-
Haemophilus influenzae R6 P14181
-
-
Streptococcus pneumoniae Q8DPI4
-
-
Streptococcus pneumoniae ATCC BAA-255 Q8DPI4
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + choline
-
 Streptococcus pneumoniae ADP + phosphocholine
-
 ?
ATP + choline
-
 Haemophilus influenzae ADP + phosphocholine
-
 ?
ATP + choline
-
 Haemophilus influenzae R6 ADP + phosphocholine
-
 ?
ATP + choline
-
 Haemophilus influenzae ATCC BAA-255 ADP + phosphocholine
-
 ?
ATP + choline
-
 Streptococcus pneumoniae ATCC BAA-255 ADP + phosphocholine
-
 ?

Synonyms

Synonyms Comment Organism
chbA
-
 Streptococcus pneumoniae
ChoK
-
 Streptococcus pneumoniae
ChoK
-
 Haemophilus influenzae
hChoK
-
 Haemophilus influenzae
LicA
-
 Streptococcus pneumoniae
LicA
-
 Haemophilus influenzae
protein LicA UniProt Haemophilus influenzae
sChoK
-
 Streptococcus pneumoniae

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0005
-
 pH and temperature not specified in the publication Streptococcus pneumoniae RSM-932A
0.197
-
 pH and temperature not specified in the publication Streptococcus pneumoniae MN58b
2.7
-
 pH and temperature not specified in the publication Streptococcus pneumoniae hemicholinium-3

General Information

General Information Comment Organism
malfunction the LTA pathway is disrupted via inhibition of sChoK with strong downstream physiological consequences affecting cell growth Streptococcus pneumoniae
metabolism the sChoK enzyme is an element of the pathway that mediates the production of teichoic acids via the intermediary CDP-choline. The elements of this pathway are expressed via thelic gene locus. The LicB gene expresses a Cho transporter, which collects Cho from the external environment. LicA codes for sChoK which phosphorylates Cho into PCho. LicC is a gene coding for cytidylyl transferase which converts PCho into CDP-choline Streptococcus pneumoniae
additional information sequence comparison of Streptococcus pneumoniae and human enzymes, overview Streptococcus pneumoniae
physiological function choline is not a nutritional requirement, but this pathogen does acquire choline from environmental sources and host cells, and produces phosphocholine which, in turn, are used to decorate lipopolysaccharides (LPS). Modified LPS molecules mediate pathogen-host cell interactions allowing the pathogen to evade the host immune system. Choline kinase (ChoK) plays a role in the growth and pathogenesis for humans of Gram-negative bacterium Haemophilus influenzae Haemophilus influenzae
physiological function 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