8AM2

Human butyrylcholinesterase in complex with 2,2'-(((1E,1'E)-(2-phenylpyrimidine-4,6-diyl)bis(methaneylylidene))bis(hydrazin-1-yl-2-ylidene))bis(N,N,N-trimethyl-2-oxoethan-1-aminium)

Summary for 8AM2

• Entry DOI: 10.2210/pdb8am2/pdb
• Descriptor: Cholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ~{N}-[(~{E})-[2-phenyl-6-[[2-[2-(trimethyl-$l^{4}-azanyl)ethanoyl]hydrazinyl]methyl]pyrimidin-4-yl]methylideneamino]-2-(trimethyl-$l^{4}-azanyl)ethanamide, ... (8 entities in total)
• Functional Keywords: inhibitor, complex, butyrylcholinesterase, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 62764.69

Authors

Nachon, F.,Brazzolotto, X.,Dias, J. (deposition date: 2022-08-02, release date: 2023-06-14, Last modification date: 2024-10-09)

Primary citation

Nachon, F.,Brazzolotto, X.,Dias, J.,Courageux, C.,Drozdz, W.,Cao, X.Y.,Stefankiewicz, A.R.,Lehn, J.M.
Grid-Type Quaternary Metallosupramolecular Compounds Inhibit Human Cholinesterases through Dynamic Multivalent Interactions.
Chembiochem, 23:e202200456-e202200456, 2022

PubMed Abstract: We report the implementation of coordination complexes containing two types of cationic moieties, i. e. pyridinium and ammonium quaternary salt, as potential inhibitors of human cholinesterase enzymes. Utilization of ligands containing NNO-coordination site and binding zinc metal ion allowed mono- and tetra-nuclear complexes to be obtained with corner and grid structural type, respectively, thus affecting the overall charge of the compounds (from +1 to +8). We were able to examine for the first time the multivalency effect of metallosupramolecular species on their inhibitory abilities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Importantly, resolution of the crystal structures of the obtained enzyme-substrate complexes provided a better understanding of the inhibition process at the molecular level.

PubMed: 36193860
DOI: 10.1002/cbic.202200456

Experimental method

X-RAY DIFFRACTION (2.5 Å)