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Title
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Mechanism of inhibition of cholinesterases by huperzine A.
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Authors
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Y.Ashani,
J.O.Peggins,
B.P.Doctor.
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Ref.
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Biochem Biophys Res Commun, 1992,
184,
719-726.
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PubMed id
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Abstract
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Huperzine A, an alkaloid isolated from Huperzia serrata was found to reversibly
inhibit acetylcholinesterases (EC 3.1.1.7) and butyrylcholinesterases (EC
3.1.1.8) with on- and off-rates that depend on both the type and the source of
enzyme. Long-term incubation of high concentrations of purified cholinesterases
(1-8 microM) with huperzine A did not show any chemical modification of
huperzine A. A low dissociation constant KI was obtained for mammalian
acetylcholinesterase-huperzine (20-40 nM) compared to mammalian
butyrylcholinesterase-huperzine (20-40 microM). This indicates that the
thermodynamic stability of huperzine-cholinesterase complex may depend on the
number and type of aromatic amino acid residues in the catalytic pocket region
of the cholinesterase molecule.
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