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PDBsum entry 2b6y
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References listed in PDB file
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Key reference
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Title
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Cooperative water filling of a nonpolar protein cavity observed by high-Pressure crystallography and simulation.
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Authors
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M.D.Collins,
G.Hummer,
M.L.Quillin,
B.W.Matthews,
S.M.Gruner.
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Ref.
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Proc Natl Acad Sci U S A, 2005,
102,
16668-16671.
[DOI no: ]
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PubMed id
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Abstract
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Formation of a water-expelling nonpolar core is the paradigm of protein folding
and stability. Although experiment largely confirms this picture, water buried
in "hydrophobic" cavities is required for the function of some
proteins. Hydration of the protein core has also been suggested as the mechanism
of pressure-induced unfolding. We therefore are led to ask whether even the most
nonpolar protein core is truly hydrophobic (i.e., water-repelling). To answer
this question we probed the hydration of an approximately 160-A(3), highly
hydrophobic cavity created by mutation in T4 lysozyme by using high-pressure
crystallography and molecular dynamics simulation. We show that application of
modest pressure causes approximately four water molecules to enter the cavity
while the protein itself remains essentially unchanged. The highly cooperative
filling is primarily due to a small change in bulk water activity, which implies
that changing solvent conditions or, equivalently, cavity polarity can
dramatically affect interior hydration of proteins and thereby influence both
protein activity and folding.
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Figure 1.
Fig. 1. Electron density in the main cavity of T4 lysozyme
mutant L99A at high pressure. Helix E is shown behind a cut-away
view of the  160-Å^3 cavity. (A)
Experimental density at 100 MPa (yellow), 150 MPa (cyan), and
200 MPa (magenta) is contoured at 0.1 electrons per Å^3.
(B) Experimental electron density at 150 MPa (cyan) compared
with simulation density at 200 MPa (magenta), contoured at 0.1
electrons per Å^3, viewed as described above. The
distribution of atoms at 100 MPa (using the occupancies of N =
1, 2, 3, 4, 5 at 200 MPa) is shown in yellow for comparison.
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Figure 3.
Fig. 3. Probability distribution (logarithmic scale) of the
number N of water molecules in the cavity from computer
simulations. Symbols show results from MD simulations at 0.1,
100, and 200 MPa. Lines are the results of perturbation theory
using the 200-MPa simulations as a reference point. Error bars
indicate statistical uncertainties corresponding to one
estimated standard deviation.
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