Last update 01 Nov 2024

CHKB

Last update 01 Nov 2024

Basic Info

Synonyms

CHETK, CHKB, CHKL

+ [11]

Introduction

Has a key role in phospholipid metabolism, and catalyzes the first step of phosphatidylethanolamine and phosphatidylcholine biosynthesis.

Drugs associated with CHKB

MN58b

Target

CHKA x CHKB

Mechanism

CHKA inhibitors [+1]

Active Org.

Instituto De Investigaciones Biomédicas De Córdoba

Originator Org.

Instituto De Investigaciones Biomédicas De Córdoba

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CHKB

100 Translational Medicine associated with CHKB

0 Patents (Medical) associated with CHKB

135

Literatures (Medical) associated with CHKB

01 Aug 2024·Life Science Alliance

Defects in integrin complex formation promoteCHKB-mediated muscular dystrophy

Article

Author: Tavasoli, Mahtab ; McMaster, Christopher R

Phosphatidylcholine (PC) is the major membrane phospholipid in most eukaryotic cells. Bi-allelic loss of function variants inCHKB, encoding the first step in the synthesis of PC, is the cause of a rostrocaudal muscular dystrophy in both humans and mice. Loss of sarcolemma integrity is a hallmark of muscular dystrophies; however, how this occurs in the absence of choline kinase function is not known. We determine that inChkb−/−mice there is a failure of the α7β1 integrin complex that is specific to affected muscle. We observed that inChkb−/−hindlimb muscles there is a decrease in sarcolemma association/abundance of the PI(4,5)P2binding integrin complex proteins vinculin, and α-actinin, and a decrease in actin association with the sarcolemma. In cells, pharmacological inhibition of choline kinase activity results in internalization of a fluorescent PI(4,5)P2reporter from discrete plasma membrane clusters at the cell surface membrane to cytosol, this corresponds with a decreased vinculin localization at plasma membrane focal adhesions that was rescued by overexpression ofCHKB.

01 Apr 2024·Journal of the European Academy of Dermatology and Venereology

Skin biopsy findings in megaconial congenital muscular dystrophy with psoriasiform lesions due to variants in CHKB

Letter

Author: Gong, Zhuoqing ; Lin, Zhimiao ; Yang, Zhou ; Wang, Huijun ; Xu, Zhe ; Chen, Kai

01 Mar 2024·Acta Parasitologica

Identification and Characterization of Entamoeba histolytica Choline Kinase

Article

Author: Chang, Chiat Han ; See Too, Wei Cun ; Few, Ling Ling ; Lim, Boon Huat

PURPOSEEntamoeba histolytica is one of the death-causing parasites in the world. Study on its lipid composition revealed that it is predominated by phosphatidylcholine and phosphatidylethanolamine. Further study revealed that its phosphorylated metabolites might be produced by the Kennedy pathway. Here, we would like to report on the characterizations of enzymes from this pathway that would provide information for the design of novel inhibitors against these enzymes in future.METHODOLOGYE. histolytica HM-1:IMSS genomic DNA was isolated and two putative choline/ethanolamine kinase genes (EhCK1 and EhCK2) were cloned and expressed from Escherichia coli BL21 strain. Enzymatic characterizations were further carried out on the purified enzymes.RESULTSEhCK1 and EhCK2 were identified from E. histolytica genome. The deduced amino acid sequences were more identical to its homologues in human (35-48%) than other organisms. The proteins were clustered as ethanolamine kinase in the constructed phylogeny tree. Sequence analysis showed that they possessed all the conserved motifs in choline kinase family: ATP-binding loop, Brenner's phosphotransferase motif, and choline kinase motif. Here, the open reading frames were cloned, expressed, and purified to apparent homogeneity. EhCK1 showed activity with choline but not ethanolamine. The biochemical characterization showed that it had a V_max of 1.9 ± 0.1 µmol/min/mg. Its K_m for choline and ATP was 203 ± 26 µM and 3.1 ± 0.4 mM, respectively. In contrast, EhCK2 enzymatic activity was only detected when Mn²⁺ was used as the co-factor instead of Mg²⁺ like other choline/ethanolamine kinases. Highly sensitive and specific antibody against EhCK1 was developed and used to confirm the endogenous EhCK1 expression using immunoblotting.CONCLUSIONSWith the understanding of EhC/EK importance in phospholipid metabolism and their unique characteristic, EhC/EK could be a potential target for future anti-amoebiasis study.

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CHKB

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