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PDBsum entry 1c6p
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Size versus polarizability in protein-Ligand interactions: binding of noble gases within engineered cavities in phage t4 lysozyme.
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Authors
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M.L.Quillin,
W.A.Breyer,
I.J.Griswold,
B.W.Matthews.
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Ref.
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J Mol Biol, 2000,
302,
955-977.
[DOI no: ]
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PubMed id
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Abstract
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To investigate the relative importance of size and polarizability in ligand
binding within proteins, we have determined the crystal structures of pseudo
wild-type and cavity-containing mutant phage T4 lysozymes in the presence of
argon, krypton, and xenon. These proteins provide a representative sample of
predominantly apolar cavities of varying size and shape. Even though the volumes
of these cavities range up to the equivalent of five xenon atoms, the noble
gases bind preferentially at highly localized sites that appear to be defined by
constrictions in the walls of the cavities, coupled with the relatively large
radii of the noble gases. The cavities within pseudo wild-type and L121A
lysozymes each bind only a single atom of noble gas, while the cavities within
mutants L133A and F153A have two independent binding sites, and the L99A cavity
has three interacting sites. The binding of noble gases within two double
mutants was studied to characterize the additivity of binding at such sites. In
general, when a cavity in a protein is created by a "large-to-small"
substitution, the surrounding residues relax somewhat to reduce the volume of
the cavity. The binding of xenon and, to a lesser degree, krypton and argon,
tend to expand the volume of the cavity and to return it closer to what it would
have been had no relaxation occurred. In nearly all cases, the extent of binding
of the noble gases follows the trend xenon>krypton>argon. Pressure
titrations of the L99A mutant have confirmed that the crystallographic
occupancies accurately reflect fractional saturation of the binding sites. The
trend in noble gas affinity can be understood in terms of the effects of size
and polarizability on the intermolecular potential. The plasticity of the
protein matrix permits repulsion due to increased ligand size to be more than
compensated for by attraction due to increased ligand polarizability. These
results have implications for the mechanism of general anesthesia, the migration
of small ligands within proteins, the detection of water molecules within apolar
cavities and the determination of crystallographic phases.
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Figure 4.
This Figure is intended to show how the shape of each cavity restricts the
motion of the noble gas and defines the preferred binding sites. The color at each
point indicates the distance from the closest point on the cavity wall. As can be seen
by comparing with Figure 1, the noble gases bind at sites that are as far as
possible from the walls of the cavity.
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The above figure is
reprinted
by permission from Elsevier:
J Mol Biol
(2000,
302,
955-977)
copyright 2000.
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Secondary reference #1
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Title
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Stabilization of phage t4 lysozyme by engineered disulfide bonds.
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Authors
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M.Matsumura,
W.J.Becktel,
M.Levitt,
B.W.Matthews.
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Ref.
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Proc Natl Acad Sci U S A, 1989,
86,
6562-6566.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Structure of bacteriophage t4 lysozyme refined at 1.7 a resolution.
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Authors
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L.H.Weaver,
B.W.Matthews.
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Ref.
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J Mol Biol, 1987,
193,
189-199.
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PubMed id
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