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PDBsum entry 1idr
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Oxygen storage/transport
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PDB id
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1idr
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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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Mycobacterium tuberculosis hemoglobin n displays a protein tunnel suited for o2 diffusion to the heme.
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Authors
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M.Milani,
A.Pesce,
Y.Ouellet,
P.Ascenzi,
M.Guertin,
M.Bolognesi.
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Ref.
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EMBO J, 2001,
20,
3902-3909.
[DOI no: ]
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PubMed id
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Abstract
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Macrophage-generated oxygen- and nitrogen-reactive species control the
development of Mycobacterium tuberculosis infection in the host. Mycobacterium
tuberculosis 'truncated hemoglobin' N (trHbN) has been related to nitric oxide
(NO) detoxification, in response to macrophage nitrosative stress, during the
bacterium latent infection stage. The three-dimensional structure of oxygenated
trHbN, solved at 1.9 A resolution, displays the two-over-two alpha-helical
sandwich fold recently characterized in two homologous truncated hemoglobins,
featuring an extra N-terminal alpha-helix and homodimeric assembly. In the
absence of a polar distal E7 residue, the O2 heme ligand is stabilized by two
hydrogen bonds to TyrB10(33). Strikingly, ligand diffusion to the heme in trHbN
may occur via an apolar tunnel/cavity system extending for approximately 28 A
through the protein matrix, connecting the heme distal cavity to two distinct
protein surface sites. This unique structural feature appears to be conserved in
several homologous truncated hemoglobins. It is proposed that in trHbN, heme
Fe/O2 stereochemistry and the protein matrix tunnel may promote O2/NO chemistry
in vivo, as a M.tuberculosis defense mechanism against macrophage nitrosative
stress.
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Figure 2.
Figure 2 (A) Ribbon stereo view of trHbN (A-chain), including
the heme group, the O[2] molecule (red) and some of the residues
deemed relevant for trHb fold stability or for trHbN
functionality. Locations of the invariant Gly-based motifs are
highlighted in yellow. Secondary structure elements are labeled
in black. All figures were drawn with MOLSCRIPT (Kraulis, 1991)
and Raster3D (Merritt and Bacon, 1997). (B) A stereo view of the
main distal and proximal site residues in trHbN, together with
the O[2] molecule (in red), the heme group, the one-turn F-helix
and segments of helices B, E and H.
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Figure 3.
Figure 3 (A) Stereo view of the protein matrix tunnel observed
in trHbN. The tunnel surface, defined by a 1.4 Å radius probe,
is portrayed in light blue. The distal site cavity surface is
calculated and displayed in the absence of the O[2] molecule,
which is, however, shown in red for reference. Residue
PheE15(62), causing the main restriction to the tunnel diameter,
is shown in black; the other residues lining the tunnel walls
are portrayed in gray. The estimated tunnel volume is  330
Å3. (B) For comparison, C-trHb protein backbone (blue) is
portrayed in the same orientation as in Figure 3A, together with
the protein matrix tunnel surface (orange), calculated as
described above. Capital letters identify selected  -helices
in the trHb fold. Both trHbs are shown approximately in the same
orientation and scale.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2001,
20,
3902-3909)
copyright 2001.
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