4B0O

Crystal structure of soman-aged human butyrylcholinesterase in complex with benzyl pyridinium-4-methyltrichloroacetimidate

Summary for 4B0O

• Entry DOI: 10.2210/pdb4b0o/pdb
• Related: 1EHO 1EHQ 1KCJ 1P0I 1P0M 1P0P 1P0Q 1XLU 1XLV 1XLW 2J4C 2WID 2WIF 2WIG 2WIJ 2WIK 2WIL 2WSL 2XMB 2XMC 2XMD 2XMG 2XQF 2XQG 2XQI 2XQJ 2XQK 2Y1K 4AQD 4AXB 4B0P
• Descriptor: CHOLINESTERASE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCINE, ... (10 entities in total)
• Functional Keywords: hydrolase, aging
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 62620.44

Authors

Wandhammer, M.,de Koning, M.,van Grol, M.,Noort, D.,Goeldner, M.,Nachon, F. (deposition date: 2012-07-04, release date: 2012-08-29, Last modification date: 2023-12-20)

Primary citation

Wandhammer, M.,De Koning, M.,Van Grol, M.,Loiodice, M.,Saurel, L.,Noort, D.,Goeldner, M.,Nachon, F.
A Step Toward the Reactivation of Aged Cholinesterases -Crystal Structure of Ligands Binding to Aged Human Butyrylcholinesterase
Chem.Biol.Interact, 203:19-, 2013

PubMed Abstract: Organophosphorus nerve agents irreversibly inhibit cholinesterases. Phosphylation of the catalytic serine can be reversed by the mean of powerful nucleophiles like oximes. But the phosphyl adduct can undergo a rapid spontaneous reaction leading to an aged enzyme, i.e., a conjugated enzyme that is no longer reactivable by oximes. One strategy to regain reactivability is to alkylate the phosphylic adduct. Specific alkylating molecules were synthesized and the crystal structures of the complexes they form with soman-aged human butyrylcholinesterase were solved. Although the compounds bind in the active site gorge of the aged enzyme, the orientation of the alkylating function appears to be unsuitable for efficient alkylation of the phosphylic adduct. However, these crystal structures provide key information to design efficient alkylators of aged-butyrylcholinesterase and specific reactivators of butyrylcholinesterase.

PubMed: 22922115
DOI: 10.1016/J.CBI.2012.08.005

Experimental method

X-RAY DIFFRACTION (2.35 Å)