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PDBsum entry 2w3h
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References listed in PDB file
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Key reference
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Title
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Structural insight into the heme-Based redox sensing by doss from mycobacterium tuberculosis.
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Authors
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H.Y.Cho,
H.J.Cho,
Y.M.Kim,
J.I.Oh,
B.S.Kang.
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Ref.
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J Biol Chem, 2009,
284,
13057-13067.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Mycobacterium tuberculosis is thought to undergo transformation into its
non-replicating persistence state under the influence of hypoxia or nitric oxide
(NO). This transformation is thought to be mediated via two sensor histidine
kinases, DosS and DosT, each of which contains two GAF domains that are
responsible for detecting oxygen tension. In this study we determined the
crystal structures of the first GAF domain (GAF-A) of DosS, which shows an
interaction with a heme. A b-type heme was embedded in a hydrophobic cavity of
the GAF-A domain and was roughly perpendicular to the beta-sheet of the GAF
domain. The heme iron was liganded by His-149 at the proximal heme axial
position. The iron, in the oxidized form, was six-coordinated with a water
molecule at the distal position. Upon reduction, the iron, in ferrous form, was
five-coordinated, and when the GAF domain was exposed to atmospheric O(2), the
ferrous form was oxidized to generate the Met form rather than a ferrous
O(2)-bound form. Because the heme is isolated inside the GAF domain, its
accessibility is restricted. However, a defined hydrogen bond network found at
the heme site could accelerate the electron transferability and would explain
why DosS was unable to bind O(2). Flavin nucleotides were shown to reduce the
heme iron of DosS while NADH was unable to do so. These results suggest that
DosS is a redox sensor and detects hypoxic conditions by its reduction.
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Figure 2.
Electron density maps around the heme at DosS GAF-A. A, water
molecule interacts with the heme iron at the distal position in
the native structure. B, ferrous iron is five coordinated in the
reduced form of GAF-A. C, upon air exposure, a water molecule
ligands the heme iron at the distal position. D, cyanide
interacts with the heme at the distal position, and Tyr-171
guides the cyanide interaction. The 2F[o]-F[c] electron density
maps were contoured at the 1.5 σ level.
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Figure 3.
Interactions of ligand and residues at the heme sites. The
numbers next to the dashed lines indicate the distances
(Å) between two atoms. The residues are water molecules at
the heme sites of the native (A), selenomethionine-substituted
(B), reduced by sodium dithionite (C) air-oxidized (D), and
cyanide complex (E) forms of DosS GAF-A. Mol-A is shown in each
of the asymmetric units of the five crystals.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
13057-13067)
copyright 2009.
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