Eichler_1994_Mol.Pharmacol_45_335

Reference

Title : Differential effects of peripheral site ligands on Torpedo and chicken acetylcholinesterase - Eichler_1994_Mol.Pharmacol_45_335
Author(s) : Eichler J , Anselmet A , Sussman JL , Massoulie J , Silman I
Ref : Molecular Pharmacology , 45 :335 , 1994
Abstract : Comparison of the effect of three 'peripheral' site ligands, propidium, d-tubocurarine, and gallamine, on acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7) of Torpedo and chicken shows that all three are substantially more effective inhibitors of the Torpedo enzyme than of the chicken enzyme. In contrast, edrophonium, which is directed to the "anionic" subsite of the active site, inhibits the chicken and Torpedo enzymes equally effectively. Two bisquaternary ligands, decamethonium and 1,5-bis(4-allydimethylammoniumphenyl)pentan-3-one dibromide, which are believed to bridge the anionic subsite of the active site and the "peripheral" anionic site, are much weaker inhibitors of the chicken enzyme than of Torpedo acetylcholinesterase, whereas the shorter bisquaternary ligand hexamethonium inhibits the two enzymes similarly. The concentration dependence of activity towards the natural substrate acetylcholine is almost identical for the two enzymes, whereas substrate inhibition of chicken acetylcholinesterase is somewhat weaker than that of the Torpedo enzyme. The experimental data can be rationalized on the basis of the three-dimensional structure of the Torpedo enzyme and alignment of the chicken and Torpedo sequences; it is suggested that the absence, in the chicken enzyme, of two aromatic residues, Tyr-70 and Trp-279, that contribute to the peripheral site of Torpedo acetylcholinesterase is responsible for the differential effects of peripheral site ligands on the two enzymes.
ESTHER : Eichler_1994_Mol.Pharmacol_45_335
PubMedSearch : Eichler_1994_Mol.Pharmacol_45_335
PubMedID: 8114681

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Citations formats

Eichler J, Anselmet A, Sussman JL, Massoulie J, Silman I (1994)
Differential effects of peripheral site ligands on Torpedo and chicken acetylcholinesterase
Molecular Pharmacology 45 :335

Eichler J, Anselmet A, Sussman JL, Massoulie J, Silman I (1994)
Molecular Pharmacology 45 :335