Title : Crystal structure of human
butyrylcholinesterase and of its complexes with substrate and products
Abstract :
- 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 Ser(198) has been modeled as bound butyrate