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PDBsum entry 1w4l
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.1.1.7
- acetylcholinesterase.
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Reaction:
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acetylcholine + H2O = choline + acetate + H+
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acetylcholine
Bound ligand (Het Group name = )
matches with 41.18% similarity
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+
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H2O
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=
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choline
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+
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acetate
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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 Am Chem Soc
126:15405-15411
(2004)
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PubMed id:
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The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design.
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H.M.Greenblatt,
C.Guillou,
D.Guénard,
A.Argaman,
S.Botti,
B.Badet,
C.Thal,
I.Silman,
J.L.Sussman.
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ABSTRACT
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Bifunctional derivatives of the alkaloid galanthamine, designed to interact with
both the active site of the enzyme acetylcholinesterase (AChE) and its
peripheral cation binding site, have been assayed with Torpedo californica AChE
(TcAChE), and the three-dimensional structures of their complexes with the
enzyme have been solved by X-ray crystallography. Differences were noted between
the IC(50) values obtained for TcAChE and those for Electrophorus electricus
AChE. These differences are ascribed to sequence differences in one or two
residues lining the active-site gorge of the enzyme. The binding of one of the
inhibitors disrupts the native conformation of one wall of the gorge, formed by
the loop Trp279-Phe290. It is proposed that flexibility of this loop may permit
the binding of inhibitors such as galanthamine, which are too bulky to penetrate
the narrow neck of the gorge formed by Tyr121 and Phe330 as seen in the crystal
structure.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.P.Colletier,
D.Bourgeois,
B.Sanson,
D.Fournier,
J.L.Sussman,
I.Silman,
and
M.Weik
(2008).
Shoot-and-Trap: use of specific x-ray damage to study structural protein dynamics by temperature-controlled cryo-crystallography.
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Proc Natl Acad Sci U S A,
105,
11742-11747.
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PDB codes:
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J.P.Colletier,
A.Royant,
A.Specht,
B.Sanson,
F.Nachon,
P.Masson,
G.Zaccai,
J.L.Sussman,
M.Goeldner,
I.Silman,
D.Bourgeois,
and
M.Weik
(2007).
Use of a 'caged' analogue to study the traffic of choline within acetylcholinesterase by kinetic crystallography.
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Acta Crystallogr D Biol Crystallogr,
63,
1115-1128.
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PDB codes:
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Z.Jin
(2007).
Amaryllidaceae and Sceletium alkaloids.
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Nat Prod Rep,
24,
886-905.
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D.A.Erlanson
(2006).
Fragment-based lead discovery: a chemical update.
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Curr Opin Biotechnol,
17,
643-652.
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G.Pastorin,
S.Marchesan,
J.Hoebeke,
T.Da Ros,
L.Ehret-Sabatier,
J.P.Briand,
M.Prato,
and
A.Bianco
(2006).
Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase.
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Org Biomol Chem,
4,
2556-2562.
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L.Alisaraie,
and
G.Fels
(2006).
Molecular docking study on the "back door" hypothesis for product clearance in acetylcholinesterase.
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J Mol Model,
12,
348-354.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
