4AXB

Crystal structure of soman-aged human butyrylcholinesterase in complex with 2-PAM

Summary for 4AXB

• Entry DOI: 10.2210/pdb4axb/pdb
• Descriptor: CHOLINESTERASE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, POTASSIUM ION, ... (9 entities in total)
• Functional Keywords: hydrolase, aging
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 62364.36

Authors

Wandhammer, M.,de Koning, M.,Noort, D.,Goeldner, M.,Nachon, F. (deposition date: 2012-06-12, 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 (2.4 Å)