3 reference(s) found. Listing paper details in reverse chronological order. We are grateful to Keith Bradnam for improvment of this script
Title: Effects of mutations of active site residues and amino acids interacting with the Omega loop on substrate activation of butyrylcholinesterase Masson P, Xie W, Froment MT, Lockridge O Ref: Biochimica & Biophysica Acta, 1544:166, 2001 : PubMed
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 allosteric effect due to binding of the second substrate molecule on the PAS. Mutation W430A was of special interest because this residue hydrogen bonds to W82 and Y332. W430A had strongly reduced affinity for tetramethylammonium. The bimolecular rate constant for reaction with diisopropyl fluorophosphate was reduced 10000-fold, indicating severe alteration in the binding area in W430A. The kcat values for butyrylthiocholine, o-nitrophenyl butyrate, and succinyldithiocholine were lower. This suggested that the mutation had caused misfolding of the active site gorge without altering the Omega loop conformation/dynamics. W430 as well as W231 and W82 appear to form the wall of the active site gorge. Mutation of any of these tryptophans disrupts the architecture of the active site.
Title: Electroconvulsive therapy and the chronic use of pseudocholinesterase- inhibitor (echothiophate iodide) eye drops for glaucoma. A case report Messer GJ, Stoudemire A, Knos G, Johnson GC Ref: General Hospital Psychiatry, 14:56, 1992 : PubMed
A case is presented in which a patient who required treatment with electroconvulsive therapy had a history of being treated with pseudocholinesterase-inhibitor eye drops (echothiophate iodide) for glaucoma. As treatment with this antiglaucoma agent contraindicated the use of succinylcholine for a minimum of 10-14 days, the short-acting nondepolarizing agent atracurium was employed instead. The anesthetic management of this patient is described as a guide for clinicians facing similar clinical situations.
Title: Kinetics of succinyldithiocholine hydrolysis by serum cholinesterase comparison to dibucaine and succinylcholine numbers Hersh LB, Raj PP, Ohlweiler D Ref: Journal of Pharmacology & Experimental Therapeutics, 189:544, 1974 : PubMed
