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The Preferable Binding Pose of Canonical Butyrylcholinesterase Substrates Is Unproductive for Echothiophate
- Source :
- Acta Naturae. 10:121-124
- Publication Year :
- 2018
- Publisher :
- Acta Naturae Ltd, 2018.
-
Abstract
- In this paper, we, for the first time, describe the interaction between the butyrylcholinesterase enzyme and echothiophate, a popular model compound and an analogue of the chemical warfare agents VX and VR, at the atomistic level. Competition between the two echothiophate conformations in the active site was found using molecular modeling techniques. The first one is close to the mode of binding of the substrates of choline series (butyrylcholine and butyrylthiocholine) and is inhibitory, since it is unable to react with the enzyme. The second one is characterized by a significantly worse estimated binding affinity and is reactive. Thus, echothiophate combines the features of two types of inhibitors: competitive and suicidal. This observation will help clarify the kinetic reaction scheme in order to accurately assess the kinetic constants, which is especially important when designing new butyrylcholinesterase variants capable of full-cycle hydrolysis of organophosphorus compounds.
- Subjects :
- 0301 basic medicine
Molecular model
biology
Echothiophate
Metadynamics
Active site
Biochemistry
Combinatorial chemistry
Butyrylthiocholine
QM/MM
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
chemistry
biology.protein
medicine
Molecular Medicine
Butyrylcholine
Molecular Biology
Butyrylcholinesterase
Biotechnology
medicine.drug
Subjects
Details
- ISSN :
- 20758251
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Acta Naturae
- Accession number :
- edsair.doi...........b15c874da539f07f0377c233ee3e0532