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PDBsum entry 2f1b
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References listed in PDB file
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Key reference
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Title
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Evaluation of docking programs for predicting binding of golgi alpha-Mannosidase ii inhibitors: a comparison with crystallography.
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Authors
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P.Englebienne,
H.Fiaux,
D.A.Kuntz,
C.R.Corbeil,
S.Gerber-Lemaire,
D.R.Rose,
N.Moitessier.
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Ref.
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Proteins, 2007,
69,
160-176.
[DOI no: ]
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PubMed id
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Abstract
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Golgi alpha-mannosidase II (GMII), a zinc-dependent glycosyl hydrolase, is a
promising target for drug development in anti-tumor therapies. Using X-ray
crystallography, we have determined the structure of Drosophila melanogaster
GMII (dGMII) complexed with three different inhibitors exhibiting IC50's ranging
from 80 to 1000 microM. These structures, along with those of seven other
available dGMII/inhibitor complexes, were then used as a basis for the
evaluation of seven docking programs (GOLD, Glide, FlexX, AutoDock, eHiTS,
LigandFit, and FITTED). We found that small inhibitors could be accurately
docked by most of the software, while docking of larger compounds (i.e., those
with extended aromatic cycles or long aliphatic chains) was more problematic.
Overall, Glide provided the best docking results, with the most accurately
predicted binding around the active site zinc atom. Further evaluation of
Glide's performance revealed its ability to extract active compounds from a
benchmark library of decoys.
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Figure 1.
Figure 1. Electron density representation of the inhibitors 8,
9 and 10 bound in the active site of dGMII. Maps are simulated
annealing omit maps (F[o]-F[c]) of only the inhibitors contoured
at 3.5  .
For orientation purposes the active site zinc ion is represented
as a magenta ball. This figure was generated with PyMOL.
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Figure 2.
Figure 2. (a) Interaction of 8 with residues in the active site
of dGMII. Interactions closer than 3.2 Å are indicated
with cyan dotted lines; interactions with the zinc ion are
indicated in magenta. Water molecules appear as orange balls.
Distances are presented in Table III. This figure was generated
with PyMOL.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2007,
69,
160-176)
copyright 2007.
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