1P0Q

Crystal structure of soman-aged human butyryl cholinesterase

Summary for 1P0Q

• Entry DOI: 10.2210/pdb1p0q/pdb
• Related: 1P0I 1P0M 1P0P
• Descriptor: Cholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: serine hydrolase, organophosphates, soman, cholinesterase, conformational change, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 61691.73

Authors

Nicolet, Y.,Lockridge, O.,Masson, P.,Fontecilla-Camps, J.C.,Nachon, F. (deposition date: 2003-04-10, release date: 2003-08-05, Last modification date: 2024-10-30)

Primary citation

Nicolet, Y.,Lockridge, O.,Masson, P.,Fontecilla-Camps, J.C.,Nachon, F.
Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products.
J.Biol.Chem., 278:41141-41147, 2003

PubMed 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.

PubMed: 12869558
DOI: 10.1074/jbc.M210241200

Experimental method

X-RAY DIFFRACTION (2.43 Å)