Structural and biochemical investigation of MARK4 inhibitory potential of cholic acid: Towards therapeutic implications in neurodegenerative diseases.
Cholic Acid
/ chemistry
Humans
Microtubules
/ chemistry
Molecular Docking Simulation
/ methods
Molecular Dynamics Simulation
Neurodegenerative Diseases
/ drug therapy
Phosphorylation
/ drug effects
Protein Binding
Protein Kinase Inhibitors
/ chemistry
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Cholic acid
Drug discovery
Kinase inhibitor
MARK4 and cancer cell lines
Molecular dynamics simulation
Journal
International journal of biological macromolecules
ISSN: 1879-0003
Titre abrégé: Int J Biol Macromol
Pays: Netherlands
ID NLM: 7909578
Informations de publication
Date de publication:
15 Oct 2020
15 Oct 2020
Historique:
received:
12
03
2020
revised:
08
06
2020
accepted:
09
06
2020
pubmed:
15
6
2020
medline:
24
3
2021
entrez:
15
6
2020
Statut:
ppublish
Résumé
Microtubule affinity regulating kinase (MARK4) is considered as a potential drug target for diabetes, cancer, and neurodegenerative diseases. Since the role of MARK4 in the phosphorylation of tau protein and subsequently Alzheimer's disease has been established, therefore, we have investigated the binding affinity and MARK4 inhibitory potential of cholic acid (CHA) using both computational and spectroscopic methods. Molecular docking suggested a strong binding of CHA to the functionally important residues of MARK4. We further performed 500 ns molecular dynamics simulation which suggested the MARK4-CHA system was quite stable throughout the simulation trajectory. CHA potential binds to the MARK4 with a binding constant (K) of 10
Identifiants
pubmed: 32535203
pii: S0141-8130(20)33520-0
doi: 10.1016/j.ijbiomac.2020.06.078
pii:
doi:
Substances chimiques
Protein Kinase Inhibitors
0
MARK4 protein, human
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Cholic Acid
G1JO7801AE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
596-604Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no competing financial interests.