6XTA

Recombinant human butyrylcholinesterase in complex with (2S)-N-[2-(1-benzylazepan-4-yl)ethyl]-2-(butylamino)-3-(1H-indol-3-yl)propanamide

Summary for 6XTA

• Entry DOI: 10.2210/pdb6xta/pdb
• Descriptor: Cholinesterase, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: butyrylcholinesterase, inhibitor, complex, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 62587.83

Authors

Brazzolotto, X.,Nachon, F.,Meden, A.,Knez, D.,Gobec, S. (deposition date: 2020-01-15, release date: 2020-10-28, Last modification date: 2024-10-16)

Primary citation

Meden, A.,Knez, D.,Malikowska-Racia, N.,Brazzolotto, X.,Nachon, F.,Svete, J.,Salat, K.,Groselj, U.,Gobec, S.
Structure-activity relationship study of tryptophan-based butyrylcholinesterase inhibitors.
Eur.J.Med.Chem., 208:112766-112766, 2020

PubMed Abstract: A series of tryptophan-based selective nanomolar butyrylcholinesterase (BChE) inhibitors was designed and synthesized. Compounds were optimized in terms of potency, selectivity, and synthetic accessibility. The crystal structure of the inhibitor 18 in complex with BChE revealed the molecular basis for its low nanomolar inhibition (IC = 2.8 nM). The favourable in vitro results enabled a first-in-animal in vivo efficacy and safety trial, which demonstrated a positive impact on fear-motivated and spatial long-term memory retrieval without any concomitant adverse motor effects. Altogether, this research culminated in a handful of new lead compounds with promising potential for symptomatic treatment of patients with Alzheimer's disease.

PubMed: 32919297
DOI: 10.1016/j.ejmech.2020.112766

Experimental method

X-RAY DIFFRACTION (2.5 Å)