Crystal Structure of Human Butyrylcholinesterase and of Its Complexes with Substrate and Products*
By Y. Nicolet, O. Lockridge, P. Masson, J. Fontecilla-Camps, F. Nachon. Journal of Biological Chemistry, 2003
750 citations recorded by the source corpus.
Cholinesterases are among the most efficient enzymes known. They are divided into two groups: acetylcholinesterase, involved in the hydrolysis of the neurotransmitter acetylcholine, and butyrylcholinesterase of unknown function. Several crystal structures of the former have shown that the active site is located at the bottom of a deep and narrow gorge, raising the question of how substrate and products enter and leave. Human butyrylcholinesterase (BChE) has attracted attention because it can hydrolyze toxic esters such as cocaine or scavenge organophosphorus pesticides and nerve agents. Here we report the crystal structures of several recombinant truncated human BChE complexes and conjugates and provide a description for mechanistically relevant non-productive substrate and product binding. As expected, the structure of BChE is similar to a previously published theoretical model of this enzyme and to the structure of Torpedo acetylcholinesterase. The main difference between the experimentally determined BChE structure and its model is found at the acyl binding pocket that is significantly bigger than expected. An electron density peak close to the catalytic Ser198 has been modeled as bound butyrate.
Subfields: Computational Theory and Mathematics, Pharmacology, Plant Science
View Paper: https://www.semanticscholar.org/paper/3d8c493ab36eb91d60fe060f5435a88d514342af
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In Computational Theory and Mathematics
Citations in the corpus
- PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. (2004, methodology): “…describing re®nement of protein±ligand complexes have successfully employed PRODRG for description of the ligand geometry (e.g. Ekstrom et al., 2002; Evans et al., 2002; Gadola et al., 2002; Hall et al., 2002; Matern et al., 2003; Nicolet et al., 2003; Zavala-Ruiz et al., 2003; Dong et al., 2004).”