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- Title
New insights into the interaction between mammalian butyrylcholinesterase and amitriptyline: a combined experimental and computational approach.
- Authors
Teralı, Kerem; Dalmizrak, Ozlem; Uzairu, Sani Muhammad; Ozer, Nazmi
- Abstract
Background: Today, there is a growing recognition in the scientific community of the many roles of butyrylcholinesterase (BChE) in both physiological and pathological contexts. Objective: Here, we aim at providing an accurate and comprehensive understanding of the mechanistic and structural aspects of mammalian BChE inhibition by the tricyclic antidepressant amitriptyline (AMI). Materials and methods: The present work involves enzyme kinetic studies as well as protein–ligand docking and interaction profiling studies. Results: We verify that AMI acts as an effective, mixed-type inhibitor of mammalian BChE, with an IC50 value of 10 μM and a Ki value of 2.25 μM. We also provide evidence showing that AMI penetrates deep into the active-site gorge of BChE where it interacts noncovalently with both the choline-binding and catalytic residues. Conclusion: These findings could facilitate the prevention of the adverse metabolic sequelae of acquired BChE deficiency and also the design of new reversible anticholinesterase drugs.
- Subjects
BUTYRYLCHOLINESTERASE; AMITRIPTYLINE; ANTIDEPRESSANTS; CHOLINESTERASE inhibitors; PROTEIN-ligand interactions
- Publication
Turkish Journal of Biochemistry / Turk Biyokimya Dergisi, 2019, Vol 44, Issue 1, p55
- ISSN
0250-4685
- Publication type
Article
- DOI
10.1515/tjb-2018-0063