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PDBsum entry 5k5e
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PDB id:
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Hydrolase
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Title:
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Discovery and structure-activity relationships of a highly selective butyrylcholinesterase inhibitor by structure-based virtual screening
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Structure:
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Cholinesterase. Chain: a, b. Synonym: acylcholine acylhydrolase,butyrylcholine esterase,choline esterase ii,pseudocholinesterase. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: bche, che1. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell_line: s2.
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Resolution:
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2.80Å
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R-factor:
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0.175
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R-free:
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0.202
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Authors:
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E.De La Mora,S.N.Dighe,G.S.Deora,B.P.Ross,F.Nachon,X.Brazzolotto
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Key ref:
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S.N.Dighe
et al.
(2016).
Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening.
J Med Chem,
59,
7683-7689.
PubMed id:
DOI:
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Date:
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23-May-16
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Release date:
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27-Jul-16
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PROCHECK
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Headers
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References
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P06276
(CHLE_HUMAN) -
Cholinesterase from Homo sapiens
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Seq:
Struc:
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602 a.a.
527 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.1.1.8
- cholinesterase.
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Reaction:
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an acylcholine + H2O = a carboxylate + choline + H+
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acylcholine
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+
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H2O
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=
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carboxylate
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+
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choline
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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J Med Chem
59:7683-7689
(2016)
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PubMed id:
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Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening.
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S.N.Dighe,
G.S.Deora,
E.De la Mora,
F.Nachon,
S.Chan,
M.O.Parat,
X.Brazzolotto,
B.P.Ross.
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ABSTRACT
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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.
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Links
