PMID: 11341926May 9, 2001Paper

Effects of mutations of active site residues and amino acids interacting with the Omega loop on substrate activation of butyrylcholinesterase

Biochimica Et Biophysica Acta
P MassonO Lockridge

Abstract

The peripheral anionic site (PAS) of human butyrylcholinesterase is involved in the mechanism of substrate activation by positively charged substrates and ligands. Two substrate binding loci, D70 in the PAS and W82 in the active site, are connected by the Omega loop. To determine whether the Omega loop plays a role in the signal transduction between the PAS and the active site, residues involved in stabilization of the loop, N83, K339 and W430, were mutated. Mutations N83A and N83Q caused loss of substrate activation, suggesting that N83 which interacts with the D70 backbone may be an element of the transducing system. The K339M and W430A mutant enzymes retained substrate activation. Residues W82, E197, and A328 in the active site gorge have been reported to be involved in substrate activation. At butyrylthiocholine concentrations greater then 2 mM, W82A showed apparent substrate activation. Mutations E197Q and E197G strongly reduced substrate activation, while mutation E197D caused a moderate effect, suggesting that the carboxylate of residue E197 is involved in substrate activation. Mutations A328F and A328Y showed no substrate activation, whereas A328G retained substrate activation. Substrate activation can result from an al...Continue Reading

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Citations

Mar 21, 2002·Biochimica Et Biophysica Acta·Patrick MassonOksana Lockridge
Feb 28, 2003·European Journal of Biochemistry·Patrick MassonOksana Lockridge
Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Brian C GeyerTsafrir S Mor
Sep 30, 2014·Biochemical Pharmacology·Herve DelacourOksana Lockridge
Jun 28, 2016·International Journal of Biological Macromolecules·Jang Hoon KimYoung Ho Kim
Feb 13, 2017·Chemico-biological Interactions·Alicia J DaffernerOksana Lockridge
Oct 28, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xavier BrazzolottoFlorian Nachon
May 23, 2018·Physical Chemistry Chemical Physics : PCCP·Xiao WanJunjun Liu
Jul 28, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Ozlem DalmizrakNazmi Ozer
Mar 27, 2019·Journal of Biomolecular Structure & Dynamics·Walter AlvaradoEric J Sorin
Sep 14, 2019·Biochimica Et Biophysica Acta. Proteins and Proteomics·Aliya R MukhametgalievaPatrick Masson
Jun 18, 2018·Archives of Biochemistry and Biophysics·Ashima SaxenaOksana Lockridge
Dec 17, 2002·Chemical Research in Toxicology·J Eric HauxJohn E Casida

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