Cholinesterases amino acid sequence

Cholinesterases (ChEs), polymorphic carboxyles-terases of broad substrate specificity, terminate neurotransmission at cholinergic synapses and neuromuscular junctions (NMJs). Being sensitive to inhibition by organophosphate (OP) poisons, ChEs belong to the serine hydrolases (B type). ChEs share 65% amino acid sequence homology and have similar molecular forms and active centre structures [1]. Substrate and inhibitor specificities classify ChEs into two subtypes ... 

Fig. 11.2. Schematic representation of the primary structure of secreted AChE B of N. brasiliensis in comparison with that of Torpedo californica, for which the three-dimensional structure has been resolved. The residues in the catalytic triad (Ser-His-Glu) are depicted with an asterisk, and the position of cysteine residues and the predicted intramolecular disulphide bonding pattern common to cholinesterases is indicated. An insertion of 17 amino acids relative to the Torpedo sequence, which would predict a novel loop at the molecular surface, is marked with a black box. The 14 aromatic residues lining the active-site gorge of the Torpedo enzyme are illustrated. Identical residues in the nematode enzyme are indicated in plain text, conservative substitutions are boxed, and non-conservative substitutions are circled. The amino acid sequence of AChE C is 90% identical to AChE B, and differs only in the features illustrated in that Thr-70 is substituted by Ser.

Lockridge, O., Bartels, C.F., Vaughan, T.A., Wong, C.K., Norton, S.E. and Johnson, L.L. (1987) Complete amino acid sequence of human serum cholinesterase. Journal of Biological Chemistry 262, 549-557. 

Butyrylcholinesterase (BChE), also known as serum cholinesterase, catalyzes the hydrolysis of butyrylcholine at rates similar to those of acetylcholine hydrolysis by AChE. Though the function of BChE is poorly understood, it shows 73% similarity and 53% amino acid sequence identity with AChE from electric eel. There is some evidence that BChE is responsible for the activation or inactivation of compounds such as heroine and cocaine and that it is involved in defense against cholinesterase inhibitors... 

G2. Gentry, M. K., and Doctor, P. B., Alignment of amino acid sequences of acetylcholinesterases and butyrylcholinesterases. In Cholinesterases Structure, Function, Mechanism, Genetics, and Cell Biology (J. Massculie, F. Bacou, E. Barnard, A. Charonnet, B. P. Doctor, and D. M. Cuinn, eds.), p. 394-398. American Chemical Society, 1991. 

There appear to be several, if not many, possible mutations which can confer various types of resistant acetylcholinesterases. Genetic approaches must be exploited to clarify this situation, including the cloning and analysis of genes for resistant acetylcholinesterases from which the critical amino acid substitutions can be discerned. To date, this gene has been cloned and sequenced from one insect, Drosophila, which was found to possess the identical active site sequence found in human, horse, and Torpedo cholinesterases ( 571-... 

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