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PDBsum entry 2fof
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References listed in PDB file
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Key reference
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Title
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Multiple solvent crystal structures: probing binding sites, Plasticity and hydration.
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Authors
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C.Mattos,
C.R.Bellamacina,
E.Peisach,
A.Pereira,
D.Vitkup,
G.A.Petsko,
D.Ringe.
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Ref.
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J Mol Biol, 2006,
357,
1471-1482.
[DOI no: ]
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PubMed id
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Abstract
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Multiple solvent crystal structures (MSCS) of porcine pancreatic elastase were
used to map the binding surface the enzyme. Crystal structures of elastase in
neat acetonitrile, 95% acetone, 55% dimethylformamide, 80% 5-hexene-1,2-diol,
80% isopropanol, 80% ethanol and 40% trifluoroethanol showed that the organic
solvent molecules clustered in the active site, were found mostly unclustered in
crystal contacts and in general did not bind elsewhere on the surface of
elastase. Mixtures of 40% benzene or 40% cyclohexane in 50% isopropanol and 10%
water showed no bound benzene or cyclohexane molecules, but did reveal bound
isopropanol. The clusters of organic solvent probe molecules coincide with
pockets occupied by known inhibitors. MSCS also reveal the areas of plasticity
within the elastase binding site and allow for the visualization of a nearly
complete first hydration shell. The pattern of organic solvent clusters
determined by MSCS for elastase is consistent with patterns for hot spots in
protein-ligand interactions determined from database analysis in general. The
MSCS method allows probing of hot spots, plasticity and hydration
simultaneously, providing a powerful complementary strategy to guide
computational methods currently in development for binding site determination,
ligand docking and design.
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Figure 1.
Figure 1. Organic solvent binding sites. Ribbon diagram of
elastase showing the binding sites for organic solvent molecules
in a common frame of reference. Each site is numbered as
described in the text. The number of the sites occupied by
organic solvent molecules in each of the models is given in
Table 2. The catalytic triad is shown explicitly in the cleft
between the two b-barrel domains: Ser203, His60, Asp108 are
shown in gray. The b-strands are shown in purple and the two
a-helices are shown in green. The organic solvent molecules are
color-coded as follows: HEX, salmon; ETH, hot pink; TFE1, cyan;
TFE2, orange; IPR, light green; IBZ, green; ICY, dark green;
ACE, red; DMF, blue; ACN, yellow. Figure 1, Figure 2, Figure 3
and Figure 4 were made using the program MOLSCRIPT.52
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Figure 4.
Figure 4. Crystallographic water molecules in the active
site. The same region of the active site is shown as in Figure 2
and Figure 3, with the same color code for protein atoms and
organic solvent molecules. Water molecules are superimposed on
the trifluoroactyl-Lys-Pro-p-isopropylanilide (pink). The water
molecules are color-coded according to the model from which they
were taken: XLINK, white; HEX, salmon; ETH, hot pink; TFE1,
cyan; TFE2, orange; IPR, light green; IBZ, green; ICY, dark
green; ACE, red; DMF, blue; ACN, yellow.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2006,
357,
1471-1482)
copyright 2006.
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