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PDBsum entry 3e5o
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Oxygen transport
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PDB id
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3e5o
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References listed in PDB file
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Key reference
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Title
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Visualizing breathing motion of internal cavities in concert with ligand migration in myoglobin.
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Authors
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A.Tomita,
T.Sato,
K.Ichiyanagi,
S.Nozawa,
H.Ichikawa,
M.Chollet,
F.Kawai,
S.Y.Park,
T.Tsuduki,
T.Yamato,
S.Y.Koshihara,
S.Adachi.
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Ref.
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Proc Natl Acad Sci U S A, 2009,
106,
2612-2616.
[DOI no: ]
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PubMed id
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Abstract
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Proteins harbor a number of cavities of relatively small volume. Although these
packing defects are associated with the thermodynamic instability of the
proteins, the cavities also play specific roles in controlling protein
functions, e.g., ligand migration and binding. This issue has been extensively
studied in a well-known protein, myoglobin (Mb). Mb reversibly binds gas ligands
at the heme site buried in the protein matrix and possesses several internal
cavities in which ligand molecules can reside. It is still an open question as
to how a ligand finds its migration pathways between the internal cavities.
Here, we report on the dynamic and sequential structural deformation of internal
cavities during the ligand migration process in Mb. Our method, the continuous
illumination of native carbonmonoxy Mb crystals with pulsed laser at cryogenic
temperatures, has revealed that the migration of the CO molecule into each
cavity induces structural changes of the amino acid residues around the cavity,
which results in the expansion of the cavity with a breathing motion. The
sequential motion of the ligand and the cavity suggests a self-opening mechanism
of the ligand migration channel arising by induced fit, which is further
supported by computational geometry analysis by the Delaunay tessellation
method. This result suggests a crucial role of the breathing motion of internal
cavities as a general mechanism of ligand migration in a protein matrix.
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Figure 1.
The crystal structures of MbCO before and after
photodissociation of CO at 40 K are superimposed and shown in
magenta and cyan, respectively. The molecular surface of MbCO
and the surface of internal cavities are shown by the mesh in
purple. The internal cavities (DP, Xe1, Xe2, Xe3, and Xe4) are
also indicated by dotted lines. The electron densities of bound
and photodissociated CO molecules in the DP are represented in
magenta and cyan, respectively, by using a 2F[o] − F[c] map
(contoured at 0.7 e/Å^3). The movement of CO, heme iron
atom, His-64, Leu-29, and His-93 after photodissociation is
shown by yellow and green arrows.
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Figure 4.
Correlated breathing motion of the internal cavities in Mb.
(A and B) Structure of MbCO at 140 K before laser illumination
(magenta) (A) and after 750-min laser illumination (cyan) (B).
The electron densities of the CO molecules in the Xe cavities
are presented by using the 2F[o] − F[c] map (contoured at 0.3
e/Å^3). The surfaces of the internal cavities are shown by
the mesh. The cavities are also outlined by dotted lines. (C)
Amino acid residues lining the DP, Xe4, Xe2, Xe1, and Xe3
cavities. The color scheme is the same as that in A and B. The
outlines of the cavities are also superimposed. The movements of
amino acid residues between the cavities are shown by yellow
arrows, and those between the Xe3 cavity and solvent area are
shown by red arrows. The white arrows represent the ligand
migration pathway between the cavities. (D) Strain tensors
calculated by using 2 coordinates without laser illumination and
after 750-min laser illumination. The strain tensors are shown
with the maximum absolute eigenvalue, and the color of the
segment shows the magnitude of the eigenvalue (blue, −0.20;
green, 0, red, +0.20). The blue segments represent contraction,
and the red segments show expansion. (E) Schematic drawing of
the correlated ligand migration in a protein.
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