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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Biochemical function
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protein binding
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1 term
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DOI no:
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Biochemistry
47:12523-12531
(2008)
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PubMed id:
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2.3 A X-ray Structure of the Heme-Bound GAF Domain of Sensory Histidine Kinase DosT of Mycobacterium tuberculosis.
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L.M.Podust,
A.Ioanoviciu,
P.R.Ortiz de Montellano.
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ABSTRACT
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Mycobacterium tuberculosis responds to changes in environmental conditions
through a two-component signaling system that detects reduced O 2 tension and NO
and CO exposures via the heme-binding GAF domains of two sensory histidine
kinases, DosT and DevS, and the transcriptional regulator DosR. We report the
first X-ray structure of the DosT heme-bound GAF domain (GAF DosT) in both oxy
and deoxy forms determined to a resolution of 2.3 A. In GAF DosT, heme binds in
an orientation orthogonal to that in the PAS domains via a highly conserved
motif, including invariant H147 as a proximal heme axial ligand. On the distal
side, invariant Y169 forms stacking interactions with the heme with its long
axis parallel and the plane of the ring orthogonal to the heme plane. In one of
the two protein monomers in an asymmetric unit, O 2 binds as a second axial
ligand to the heme iron and is stabilized via a H-bond to the OH group of Y169.
The structure reveals two small tunnel-connected cavities and a pore on the
protein surface that suggest a potential route for the access of O 2 to the
sensing pocket. The limited conformational differences observed between
differently heme iron-ligated GAF DosT monomers in the asymmetric unit may
result from crystal lattice limitations since atmospheric oxygen binding likely
occurs in the crystal as a result of X-ray-induced Fe (3+) photoreduction during
diffraction data collection. Determination of the GAF DosT structure sets up a
framework in which to address ligand recognition, discrimination, and signal
propagation schemes in the heme-based GAF domains of biological sensors.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Perry,
K.Koteva,
and
G.Wright
(2011).
Receptor domains of two-component signal transduction systems.
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Mol Biosyst, 7,
1388-1398.
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J.Cheung,
and
W.A.Hendrickson
(2010).
Sensor domains of two-component regulatory systems.
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Curr Opin Microbiol, 13,
116-123.
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J.Lacal,
C.García-Fontana,
F.Muñoz-Martínez,
J.L.Ramos,
and
T.Krell
(2010).
Sensing of environmental signals: classification of chemoreceptors according to the size of their ligand binding regions.
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Environ Microbiol, 12,
2873-2884.
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M.J.Kim,
K.J.Park,
I.J.Ko,
Y.M.Kim,
and
J.I.Oh
(2010).
Different roles of DosS and DosT in the hypoxic adaptation of Mycobacteria.
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J Bacteriol, 192,
4868-4875.
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A.Ioanoviciu,
Y.T.Meharenna,
T.L.Poulos,
and
P.R.Ortiz de Montellano
(2009).
DevS oxy complex stability identifies this heme protein as a gas sensor in Mycobacterium tuberculosis dormancy.
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Biochemistry, 48,
5839-5848.
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A.Möglich,
R.A.Ayers,
and
K.Moffat
(2009).
Structure and signaling mechanism of Per-ARNT-Sim domains.
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Structure, 17,
1282-1294.
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H.Y.Cho,
H.J.Cho,
Y.M.Kim,
J.I.Oh,
and
B.S.Kang
(2009).
Structural Insight into the Heme-based Redox Sensing by DosS from Mycobacterium tuberculosis.
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J Biol Chem, 284,
13057-13067.
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PDB codes:
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R.Gao,
and
A.M.Stock
(2009).
Biological insights from structures of two-component proteins.
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Annu Rev Microbiol, 63,
133-154.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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