A steric blockade model for inhibition of acetylcholinesterase by peripheral site ligands and substrate

Chemico-Biological Interactions

Volumn 119-120, Issue , 1999, Pages 85-97

  Rosenberry, Terrone L ^a   Mallender, William D ^a   Thomas, Patrick J ^b   Szegletes, Tivadar ^a  

^a MAYO CLINIC   (United States)

^b CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Acetylcholinesterase; Fasciculin; Nonequilibrium enzyme kinetics; Organophosphate; Propidium

Indexed keywords

ACETYLCHOLINESTERASE; ACETYLTHIOCHOLINE; FASCICULIN; PROPIDIUM IODIDE;

ASSOCIATION; CONFERENCE PAPER; CONFORMATIONAL TRANSITION; DISSOCIATION CONSTANT; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME SPECIFICITY; HUMAN; HUMAN CELL; LIGAND BINDING; PROTEIN PHOSPHORYLATION;

ACETYLCHOLINE; ACETYLCHOLINESTERASE; BINDING SITES; CHOLINESTERASE INHIBITORS; ERYTHROCYTES; HUMANS; HYDROLYSIS; INDICATORS AND REAGENTS; KINETICS; LIGANDS; MODELS, CHEMICAL; PHOSPHORYLATION; PROPIDIUM; PROTEIN CONFORMATION; STEREOISOMERISM; SUBSTRATE SPECIFICITY;

EID: 0032998176     PISSN: 00092797     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0009-2797(99)00017-4     Document Type: Conference Paper

References (17)

1. Taylor P., Lappi S. Interaction of fluorescence probes with acetylcholinesterase. The site and specificity of propidium binding. Biochemistry. 14:1975;1989-1997.
2. Szegletes T., Mallender W.D., Rosenberry T.L. Nonequilibrium analysis alters the mechanistic interpretation of inhibition of acetylcholinesterase by peripheral site ligands. Biochemistry. 37:1998;4206-4216.
3. Rosenberry T.L., Scoggin D.M. Structure of human erythrocyte acetylcholinesterase. Characterization of intersubunit disulfide bonding and detergent interaction. J. Biol. Chem. 259:1984;5643-5652.
4. J.B.S. Haldane, Enzymes, Longmans, Green, New York, 1930, pp. 84.
5. Eastman J., Wilson E.J., Cervenansky C., Rosenberry T.L. Fasciculin 2 binds to a peripheral site on acetylcholinesterase and inhibits substrate hydrolysis by slowing a step involving proton transfer during enzyme acylation. J. Biol. Chem. 270:1995;19694-19701.
6. Nachmansohn D., Wilson I.B. Enzymic hydrolysis and synthesis of acetylcholine. Adv. Enzymol. 12:1951;259-339.
7. Szegletes T., Mallender W.D., Thomas P.J., Rosenberry T.L. Substrate binding to the peripheral site of acetylcholinesterase initiates enzymatic catalysis. Substrate inhibition arises as a secondary effect. Biochemistry. 38:1999;122-133.
8. Prince A.K. Spectrophotometric study of the acetylcholinesterase-catalyzed hydrolysis of 1-methyl-acetoxyquinolinium iodides. Arch. Biochem. Biophys. 113:1966;195-204.
9. Rosenberry T.L., Bernhard S.A. Studies on catalysis by acetylcholinesterase: synergistic effects of inhibitors during hydrolysis of acetic acid esters. Biochemistry. 11:1972;4308-4321.
10. Krupka R.M., Laidler K.J. Molecular mechanisms for hydrolytic enzyme action. II. Inhibition of acetylcholinesterase by excess substrate. J. Am. Chem. Soc. 83:1961;1448-1454.
11. Zeller E.A., Bissegger A. Uber die Cholinesterase des Gehirns und der Erythrocyten. Helv. Chim. Acta. 26:1943;1619-1630.
12. Aldridge W.N., Reiner E. Acetylcholinesterase: two types of inhibition by an organophosphorus compound: one the formation of phosphorylated enzyme and the other analogous to inhibition by substrate. Biochem. J. 115:1969;147-162.
13. Radic Z., Reiner E., Taylor P. Role of the peripheral anionic site on acetylcholinesterase: inhibition by substrates and coumarin derivatives. Mol. Pharmacol. 39:1991;98-104.
14. Rosenberry T.L. Quantitative simulation of endplate currents at neuromuscular junctions based on the reactions of acetylcholine with acetylcholine receptor and acetylcholinesterase. Biophys. J. 26:1979;263-290.
15. 125I-fasciculin to rat brain acetylcholinesterase. The complex still binds diisopropyl fluorophosphate. J. Biol. Chem. 268:1993;12458-12467.
16. Rosenberry T.L., Rabl C.R., Neumann E. Binding of the neurotoxin fasciculin 2 to the acetylcholinesterase peripheral site drastically reduces the association and dissociation rate constants for N-methylacridinium binding to the active site. Biochemistry. 35:1996;685-690.
17. Mallender W.D., Szegletes T., Rosenberry T.L. Organophosphorylation of acetylcholinesterase in the presence of peripheral site ligands: distinct effects of propidium and fasciculin. J. Biol. Chem. 274:1999;8491-8499.