Insights into substrate and product traffic in the Drosophila melanogaster acetylcholinesterase active site gorge by enlarging a back channel

The FEBS Journal
Florian NachonDidier Fournier

Abstract

To test a product exit differing from the substrate entrance in the active site of acetylcholinesterase (EC 3.1.1.7), we enlarged a channel located at the bottom of the active site gorge in the Drosophila enzyme. Mutation of Trp83 to Ala or Glu widens the channel from 5 A to 9 A. The kinetics of substrate hydrolysis and the effect of ligands that close the main entrance suggest that the mutations facilitate both product exit and substrate entrance. Thus, in the wild-type, the channel is so narrow that the 'back door' is used by at most 5% of the traffic, with the majority of traffic passing through the main entrance. In mutants Trp83Ala and Trp83Glu, ligands that close the main entrance do not inhibit substrate hydrolysis because the traffic can pass via an alternative route, presumably the enlarged back channel.

References

Sep 1, 1995·The Journal of Biological Chemistry·Z RadićP Taylor
Aug 30, 1994·Biochemical and Biophysical Research Communications·H ChaabihiM Cérutti
Mar 31, 1998·Protein Expression and Purification·S Estrada-Mondaca, D Fournier
Sep 22, 2000·Analytical Biochemistry·A CharpentierD Fournier
Mar 30, 2001·The Journal of Biological Chemistry·L BrochierD Fournier
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE
Mar 20, 2004·European Journal of Biochemistry·Jure StojanDidier Fournier
Jun 10, 2006·The EMBO Journal·Jacques-Philippe ColletierMartin Weik
Nov 17, 2007·Acta Crystallographica. Section D, Biological Crystallography·Jacques-Philippe ColletierMartin Weik

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Citations

Dec 31, 2010·Cellular and Molecular Life Sciences : CMLS·James S Fraser, Colin J Jackson
Mar 19, 2009·The FEBS Journal·Markus PietschMichael Gütschow
May 16, 2017·Journal of Neurochemistry·Israel Silman, Joel L Sussman
Aug 11, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yechun XuHualiang Jiang
Jan 4, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yves Bourne, Pascale Marchot
Apr 15, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mihai V Putz
Dec 31, 2019·Mini Reviews in Medicinal Chemistry·Kiran BagriParvin Kumar
May 1, 2021·Biomolecules·Danna De BoerEric J Sorin

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