PDBsum entry 5k5e

Hydrolase

PDB id: 5k5e

Contents

Protein chains

527 a.a.

Ligands

NAG-NAG ×3

NAG ×10

6QS ×2

EDO ×3

GOL ×2

Waters ×127

References listed in PDB file

Key reference

• Title: Discovery and structure-Activity relationships of a highly selective butyrylcholinesterase inhibitor by structure-Based virtual screening.
• Authors: S.N.Dighe, G.S.Deora, E.De la mora, F.Nachon, S.Chan, M.O.Parat, X.Brazzolotto, B.P.Ross.
• Ref.: J Med Chem, 2016, 59, 7683-7689. [DOI no: 10.1021/acs.jmedchem.6b00356]
• PubMed id: 27405689

Abstract

Structure-based virtual screening of two libraries containing 567 981 molecules was used to discover novel, selective BuChE inhibitors, which are potentially superior symptomatic treatments in late-stage Alzheimer's disease. Compound 16 was identified as a highly selective submicromolar inhibitor of BuChE (huBuChE IC50 = 0.443 μM) with high permeability in the PAMPA-BBB model. The X-ray crystal structure of huBuChE in complex with 16 revealed the atomic-level interactions and offers opportunities for further development of the series.