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PDBsum entry 1v9y
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Signaling protein
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PDB id
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1v9y
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Contents |
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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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A redox-Controlled molecular switch revealed by the crystal structure of a bacterial heme pas sensor.
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Authors
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H.Kurokawa,
D.S.Lee,
M.Watanabe,
I.Sagami,
B.Mikami,
C.S.Raman,
T.Shimizu.
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Ref.
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J Biol Chem, 2004,
279,
20186-20193.
[DOI no: ]
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PubMed id
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Abstract
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PAS domains, which have been identified in over 1100 proteins from all three
kingdoms of life, convert various input stimuli into signals that propagate to
downstream components by modifying protein-protein interactions. One such
protein is the Escherichia coli redox sensor, Ec DOS, a phosphodiesterase that
degrades cyclic adenosine monophosphate in a redox-dependent manner. Here we
report the crystal structures of the heme PAS domain of Ec DOS in both inactive
Fe(3+) and active Fe(2+) forms at 1.32 and 1.9 A resolution, respectively. The
protein folds into a characteristic PAS domain structure and forms a homodimer.
In the Fe(3+) form, the heme iron is ligated to a His-77 side chain and a water
molecule. Heme iron reduction is accompanied by heme-ligand switching from the
water molecule to a side chain of Met-95 from the FG loop. Concomitantly, the
flexible FG loop is significantly rigidified, along with a change in the
hydrogen bonding pattern and rotation of subunits relative to each other. The
present data led us to propose a novel redox-regulated molecular switch in which
local heme-ligand switching may trigger a global "scissor-type"
subunit movement that facilitates catalytic control.
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Figure 2.
FIG. 2. Dimer of Ec DOSH and redox-induced changes at the
heme distal site. a, left, Fe^3+ form of the Ec DOSH dimer. The
2-fold axis of subunits is specified as a blue stick. Right, the
view after 90° rotation of the left figure. Heme and
proximal histidine 77 are shown as a ball-and-stick model.
Disordered FG loop regions are indicated by blue broken lines.
Water molecules are represented by spheres (cyan). N, N
terminus; C, C terminus. b, close-up view of the heme site of
the Fe^3+ form of Ec DOSH (left); the same region of the Fe^2+
form (right). FG loop regions are rigidified in the Fe^2+ form
(cyan). The distal axial ligand is replaced by Met-95, as
indicated in the sphere model.
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Figure 4.
FIG. 4. Reorganization of the hydrogen bond network at the
heme distal site near the dimer interface. a, comparison of heme
distal sites between Fe^3+ (cyan) and Fe^2+ (yellow) forms of Ec
DOSH. Residues 31-85 and 97-132 of subunit I in each form were
superimposed. Residues in subunit II are colored in blue for the
Fe^3+ form and orange for the Fe^2+ form. Hydrogen bonds are
presented as dotted lines. Met-95 coordination to the heme iron
upon reduction induces reorganization of the hydrogen bond
network at the heme distal site. Side chains of Phe-113 and
Leu-115 move slightly to adjust to heme-ligand switching. These
changes induce hydrogen bond formation between Phe-113 and
Arg-131. No effects were observed on the hydrogen bond between
Ser-116 and Met-30. The buried dimer surface areas of the Fe^3+
form (b) and Fe^2+ form (c) of subunit I are shown. Distances
between the surfaces of each subunit were calculated with MOLMOL
and ranged from <2 Å (red) to >7 Å (blue). Met-30
and Arg-131 of subunit II are presented as a stick model.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
20186-20193)
copyright 2004.
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