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Originally published In Press as doi:10.1074/jbc.R100058200 on November 5, 2001
J. Biol. Chem., Vol. 277, Issue 2, 871-874, January 11, 2002
MINIREVIEW
Truncated Hemoglobins: A New Family of Hemoglobins Widely
Distributed in Bacteria, Unicellular Eukaryotes, and
Plants*,
Jonathan B.
Wittenberg §,
Martino
Bolognesi¶,
Beatrice A.
Wittenberg , and
Michel
Guertin
From the Department of Physiology and Biophysics,
Albert Einstein College of Medicine, Bronx, New York 10461, ¶ Department of Physics, INFM and Advanced Biotechnology Center,
IST, University of Genova, Largo Rosanna Benzi 10, 16132 Genova, Italy,
and Departement de Biochimie et Microbiologie, Pavillon
Marchand, Universite Laval, Quebec G1K 7P4, Canada
 |
INTRODUCTION |
Truncated hemoglobins
(trHbs)1 (1) constitute a
family of small oxygen-binding heme proteins distributed in eubacteria, cyanobacteria, protozoa, and plants (Table I, Supplemental Material) forming a distinct group within the hemoglobin (Hb) superfamily (2).
They are nearly ubiquitous in the plant kingdom, occur in many
aggressively pathogenic bacteria, and are held to be of very ancient
origin. None have been detected in the genomes of archaea or metazoa.
Characteristically, trHbs occur at nano- to micromolar intracellular
concentration, hinting at a possible role as catalytic proteins.
Many trHbs display amino acid sequences 20-40 residues shorter than
non-vertebrate hemoglobins to which they are scarcely related by
sequence similarity. Crystal structures (1, 3) show that trHb tertiary
structure is based on a 2-on-2 -helical sandwich, which represents
an unprecedented editing of the highly conserved globin fold. Moreover,
an almost continuous hydrophobic tunnel, traversing the protein matrix
from the molecular surface to the heme distal site, may provide a path
for ligand diffusion to the heme.
 |
trHbs Are Phylogenetically Distinct within the Hb
Superfamily |
More than 40 putative trHb genes have been identified (Table I,
Supplemental Material). A phylogenetic analysis (Fig.
1) indicates that trHbs form a distinct
family separate from bacterial flavohemoglobins, Vitreoscilla Hb, plant symbiotic and non-symbiotic
hemoglobins, and animal hemoglobins. Notably, trHb genes and
flavohemoglobin genes frequently coexist in the same bacterium (Table
I, Supplemental Material), suggesting distinct functions for each.
Three distinct groups (groups I, II, and III) can be distinguished
within the trHb family with four clusters within group II. The extent
of amino acid identity between members of the different groups,
e.g. Mycobacterium tuberculosis trHbO (group II)
and trHbN (group I), can be low (18%) (Fig. 1, Supplemental Material).
However, identity rises dramatically when the M. tuberculosis trHbO sequence is compared with the orthologue
sequences from Mycobacterium avium (84%),
Mycobacterium leprae (83%), Cornybacterium
diphterae (64%), and Streptomyces coelicolor (66%) or
when the M. tuberculosis trHbN is compared with its M. avium orthologue (79%). The presence of trHb genes from groups I,
II, and III in M. avium (Gram-positive) and in
Methylococcus capsulatus (proteobacteria) may indicate that
the different trHb lineages diverged from their last common ancestor
before the separation of the main prokaryotic lineages (Fig. 1).

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Fig. 1.
Phylogenetic tree showing the
relationships among trHbs. The distance tree (minimum evolution
method) was constructed using the PAUP program (version 4.0b1).
Bootstrap values were calculated from 1000 replicates. Important
residues (B9, B10, CD1, E7, E14, and F8) with regard to coordination of
the heme and the ligand binding residue properties are indicated. The
sequences alignment used for the cladistic analysis is shown in
Supplemental Material (Fig. 1).
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An interesting progression is found in the genus
Mycobacterium. The genome of the opportunistic pathogen,
M. avium, contains one trHb from each group of the family,
trHbP (group III), trHbO (group II), and trHbN (group I) (Fig. 1). The
facultative intracellular pathogen, M. tuberculosis, that
infects man, has two, trHbN and trHbO, and the obligate intracellular
pathogen, M. leprae, which has undergone extensive reductive
evolution and is thought to have only a minimal gene set for a
pathogenic mycobacterium (4), retains solely trHbO, which accordingly
may play an essential role.
 |
The 2-on-2 -Helical Fold Characterizes trHbs |
Crystal structures of trHbs from Chlamydomonas
eugametos, Paramecium caudatum, and M. tuberculosis show that their three-dimensional fold is based on a
subset of the classical globin fold (the so-called 3-on-3 -helical
sandwich). In trHbs the antiparallel helix pairs B/E and G/H are the
main secondary structure elements arranged in a 2-on-2 sandwich (1, 3)
(Fig. 2). Within the trHb fold the
N-terminal A helix is almost completely deleted, and the whole CD-D
region is trimmed to about 3 residues, possibly the minimum polypeptide
stretch to bridge between C- and E-helices. Moreover, most of the
heme-proximal F-helix is substituted by a polypeptide segment (pre-F)
in extended conformation, followed by the one-turn F-helix that
properly supports the HisF8 residue, allowing heme iron coordination.
Thus, the trHb polypeptide chain is not simply a truncated version of a
conventionally folded globin. Rather, it owes its conformational
stability to residue deletions and substitutions at specific sites, as
compared with non-vertebrate globins (1, 3).

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Fig. 2.
A structural overlay of C. eugametos trHb (red ribbons) on
sperm whale Mb (green), the latter taken as the
prototype of the (non)-vertebrate globin fold. N and C termini are
labeled for C. eugametos trHb. This and similar structural
comparisons with other (non)-vertebrate Hbs or Mbs indicate that the
match between 2-on-2 trHbs and 3-on-3 globins is limited to less than
60 C pairs, mostly located on the distal side of the
heme (right in the figure). The main trHb -helical
segments are labeled according to the topological conventions defined
for the 3-on-3 globin fold (16).
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Specific sequence motifs support attainment of the compact trHb fold.
Among these, three glycine motifs (present in groups I and II), located
at the AB and EF interhelical corners and immediately before the
one-turn F-helix, help the pre-F segment to build a properly structured
heme crevice within a very short polypeptide chain. Heme isomerism has
been reported in trHbs (1, 5).
Very few amino acids are strictly conserved throughout the known trHb
sequences, the proximal HisF8 being the only invariant residue. A
Phe-Tyr pair is strongly conserved at the B9-B10 sites, where Tyr-B10
participates in heme ligand stabilization. Site CD1, invariably Phe in
non-vertebrate Hbs, hosts Phe, Tyr, or His, whereas at least six
different residue types occupy the distal E7 position. Moreover, the
almost invariant Phe-E14, located along the heme distal face, may be
related to a heme/solvent shielding role together with apolar residues
of the pre-F segment.
 |
Heme Coordination |
Distal pocket residues may ligate the heme iron to form
6-coordinate, low spin, structures. Residue Tyr-B10 has been suggested to play this role in ferric C. eugametos trHb (6); His-E10 of Synechocystis sp. trHb may ligate the iron of ferric and
ferrous species (7-9). These structures are in equilibrium with
5-coordinate or aquoferric forms with which exogenous ligands react. At
high ligand concentration, where conversion of the 6- to the
5-coordinate form becomes rate-limiting, the rates of ligand
combination give a measure of the rate of conversion (9, 10). If this
rate is low, about 30 s 1 as in Synechocystis
sp. trHb (7, 9), the 6-coordinate form is strongly favored. In the
instance of C. eugametos trHb, where the rate of this
conversion in the ferrous alkaline form is 5-fold higher, 6- or
5-coordinate species prevail at different pH (10). Five-coordinate,
high spin ferrous species of P. caudatum (11), M. tuberculosis trHbN (12), and M. tuberculosis
trHbO2 predominate at all pH.
A 6-coordinate form of Arabidopsis thaliana deoxy-trHb is
short-lived and reverts to a 5-coordinate species (13).
In the known trHb three-dimensional structures the proximal His-F8
imidazole ring is markedly staggered relative to the heme pyrrole N
atoms (1, 3, 14). This together with the high value of His-F8 NE2-Fe
stretching frequencies (220-232 cm 1) (10, 11,
15)3 indicates an unstrained
proximal His, whose coordination to the heme iron facilitates a heme
in-plane location of the iron atom that in turn supports fast oxygen
association and electron donation to the bound distal ligand (16).
Moreover, the O-O stretching frequencies measured for oxygenated
C. eugametos, Synechocystis sp., and M. tuberculosis trHbO (1136, 1133, and 1140 cm 1,
respectively) (17)2 are consistent with a ferric superoxide
character of the heme-ligand pair.
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Networks of Hydrogen Bonds Stabilize the Heme Distal
Ligand |
The heme distal site of trHb is characterized by the nearly
invariant Tyr-B10, the main residue providing direct hydrogen bonding
to the heme-bound ligand (as observed in aquo-Met P. caudatum trHb, cyano-Met C. eugametos trHb, and
M. tuberculosis oxy-trHbN (1, 3, 11) (see Fig.
3). A distal network of H-bonds has been
shown to stabilize the ligated O2 in M. tuberculosis trHbN (with Leu at the E7 site) through direct
interaction with the Tyr-B10 phenolic oxygen atom and hydrogen bonding
of this oxygen atom to Gln-E11 (3).3 Analysis of the
crystal structures shows that distal site networks based on Tyr-B10
ligand and Tyr-B10-Gln/Thr-E11 hydrogen bonds are conserved in ferric
cyano-Met C. eugametos and aquo-Met P. caudatum
trHbs, respectively (1). Additionally, the latter ferric trHbs display
hydrogen bonds between Gln-E7 and the heme ligand, indicating that
polar E7 residues are effective in ligand stabilization and that
hydrogen bonding between E7 and Tyr-B10 may also contribute to
effective structuring of the distal site residues. In this respect, it
should be noted that the occurrence of small apolar residues (Ala, Gly)
at the E7 site may be compensated by CD1 Phe-224 Tyr/His mutations such
as observed in different trHbs of group II (Fig. 1, Supplemental
Material).

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Fig. 3.
A view of the distal site cavity in M. tuberculosis oxy-trHbN in an orientation close to that of
Fig. 2. The heme group is edge-on and the iron atom is shown as a
purple sphere; the iron-coordinated
O2 molecule is displayed in red. Distal site
residues and the proximal histidine are labeled according to their
topological sites. The CD segment and part of the B- and of the
E-helices are displayed as cyan ribbons.
Dashed lines highlight the hydrogen-bonded
interactions stabilizing the ligand in the distal site.
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The role played by residues Tyr-B10 and Gln-E7 in ligand stabilization
is further stressed by mutational studies (10, 12, 15) and by results
of Das et al. (17) on the simultaneously observed O-O and
Fe-O stretching frequencies in C. eugametos and Synechocystis sp. trHbs. It should also be noticed that the
trHb hydrogen-bonded network centered on Tyr-B10 is strongly
reminiscent of that observed for the very high oxygen affinity Hb from
the nematode Ascaris suum (18, 19). In these cases,
extraordinarily low oxygen dissociation rates (0.004-0.0014
s 1) result in a high oxygen affinity (0.004-0.005 mm Hg)
(9, 10, 20).
The Fe-OO stretching frequency of P. caudatum oxy-trHb
detected by resonance Raman spectroscopy indicates strong polar
interactions (including hydrogen bonding) between the bound ligand and
the nearby Tyr-B10 residue, implying slow dissociation and high ligand affinity (11). In addition, the two Fe-CO stretching frequencies observed in the resonance Raman spectra of both M. tuberculosis trHbN-CO and Ascaris Hb-CO derivatives
indicate two conformers expected to display slow and rapid ligand
dissociation rates, respectively (15, 21). The actual dissociation of
bound O2 or CO is attributed to a fast equilibrium between
two conformers, with the ligand off-rate being determined either by the
rate of conformer interconversion or by ligand dissociation from the
conformer with the higher rate.
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Ligands Can Enter the Distal Heme Pocket through a Protein
Matrix Tunnel |
Because of the orientation of the CD-D region, the E-helix of trHb
falls close to the distal face of the heme. Crowding by distal residues
and their interactions with the heme block access to the distal site
cavity through the classical E7 residue gate, typically achieved in
vertebrate Hbs by His-E7 (22-25). Remarkably, however, a different
route for ligand diffusion to/from the heme appears to be coded in trHb
structures as a cavity network or tunnel through the protein matrix. In
C. eugametos trHb and M. tuberculosis trHbN, the
tunnel is composed of two roughly orthogonal branches converging at the
heme distal site from two distinct protein surface access sites. On one
hand, a 20-Å long tunnel branch connects the globin region nestled
between the AB and GH corners to the heme distal site. On the other, a
path of about 8 Å connects an opening in the protein structure between
G- and H-helices to the heme. The tunnel branches display inner
diameters in the 5-7 Å range for a ligand-accessible volume of
330-360 Å3 (1, 3). Residues lining the tunnel branches
are hydrophobic and are substantially conserved throughout the trHb
family, suggesting that the tunnel plays a functional role and is
suited for small nonpolar ligand diffusion or storage. A study of
ligand rebinding following photolysis of CO in C. eugametos
or P. caudatum
trHbs4 suggests that the
tunnel/cavity network in these proteins may indeed act as a CO store
whose filling strikingly affects ligand rebinding kinetics.
Protein cavities, accessible to xenon atoms in Mb, have been shown to
act dynamically as CO secondary docking sites. This has led to the
suggestion that protein cavities modulate ligand dynamics and
reactivity (Refs. 26 and 27, and references therein). On the other
hand, protein matrix tunnels connect the surface to active sites in
Ni-Fe hydrogenases (28), in methane monooxygenase hydroxylase (29), and
in carbon monoxide dehydrogenase (30). Tunnels serve for internal
substrate translocation in some enzymes (31). Different residues may
modulate ligand diffusion processes along the trHb tunnel. For
instance, Phe-E15 of M. tuberculosis trHbN is observed in
two distinct conformations in the crystal structure and may act as a
gate controlling ligand diffusion along the main tunnel branch (3).
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trHbs Serve Diverse Functions |
The functional roles of trHbs are little known and may be various.
The trHb of the unicellular green alga C. eugametos is induced in response to active photosynthesis and is localized, in part,
along the chloroplast thylakoid membranes (32). The soluble trHb of the
cyanobacterium Nostoc commune is localized on the
cytoplasmic face of the cell membrane and is expressed only under
anaerobic conditions (33, 34). In addition, the gene encoding this trHb
is coexpressed with genes of the nitrogen fixation complex (34). Oxygen
supply to the mitochondria of the protozoan Paramecium is
impeded by levels of CO sufficient to block trHb but not cytochrome
oxidase (35).
There is a great deal of evidence that NO generated by nitric-oxide
synthase II in macrophages controls the development of M. tuberculosis infection in mouse and man and restricts the bacteria to a latent state (36). However, tuberculous infection is in a dynamic
balance that teeters for years in a competition between host immunity
and M. tuberculosis growth, indicating the presence of an
endogenous mechanism for NO resistance in the tubercle bacillus. That
the oxygenated form of trHbN may be involved in the protection of the
bacilli against NO produced in the granuloma during latency is
supported by the observation that Mycobacterium bovis BCG
cells that no longer express trHbN are severely impaired in their
ability to metabolize NO in
vitro.5 Oxy-trHbN could
scavenge NO in vitro by promoting dioxygenation as observed
in human oxy-Hb, oxy-Mb, and Escherichia coli
flavohemoglobin, in which NO is converted to nitrate by reaction with
the oxygenated heme (37-39).
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Conclusion |
The currently available data indicate that the dramatically
simplified 2-on-2 version of the globin fold observed in trHbs may
reflect biological functions distinct from O2 storage or
transport. In particular, the combination of a closed distal site with
the presence of an elongated protein matrix tunnel hints at internal ligand diffusion mechanisms different from those based on the E7 distal
gate in Mb. Whereas packing defects observed in Mb are used as ligand
secondary docking sites, the trHb protein matrix tunnel may prove
crucial not only for heme accessibility but also for local storage of
O2 molecules. Notably, although packing defects in Mb and
the tunnel system in trHbs may appear evolutionarily related, their
topology and size, relative to the globin fold, are drastically
different. The above considerations highlight a previously unpredicted
structural plasticity of the globin fold, presenting us with new
general concepts on Hb structure and focusing our interests on
potentially new functions within the Hb superfamily.
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FOOTNOTES |
*
This minireview will be reprinted
in the 2002 Minireview Compendium, which
will be available in December, 2002.
The on-line version of this article (available at
http://www.jbc.org) contains a supplemental table and a
supplemental figure.
§
To whom correspondence should be addressed. Tel.: 718-430-2064;
Fax: 718-430-8819; E-mail: bwitten@aecom.yu.edu.
Published, JBC Papers in Press, November 5, 2001, DOI 10.1074/jbc.R100058200
2
M. Guertin and S. R. Yeh, unpublished observations.
3
Although M. tuberculosis trHbN was
originally proposed to be a cooperative dimer with n = 2 (12), ongoing investigations indicate that oxygenation of this trHb
may not be cooperative (M. Guertin, unpublished observations).
4
U. Samuni, D. Dansker, A. Ray, L. Moens, M. Guertin, and J. F. Friedman, manuscript in preparation.
5
M. Guertin, unpublished results.
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ABBREVIATIONS |
The abbreviations used are:
trHb, truncated
hemoglobin;
Hb, hemoglobin;
Mb, myoglobin.
 |
REFERENCES |
| 1.
|
Pesce, A.,
Couture, M.,
Dewilde, S.,
Guertin, M.,
Yamauchi, K.,
Ascenzi, P.,
Moens, L.,
and Bolognesi, M.
(2000)
EMBO J.
19,
2424-2434
|
| 2.
|
Moens, L.,
Vanfleterin, J.,
Van de Peer, Y.,
Peeters, K.,
Kapp, O.,
Czelusniak, J.,
Goodman, M.,
and Vinogradov, S. N.
(1996)
Mol. Biol. Evol
13,
324-333
|
| 3.
|
Milani, M.,
Pesce, A.,
Ouellet, Y.,
Ascenzi, P.,
Guertin, M.,
and Bolognesi, M.
(2001)
EMBO J.
20,
3902-3909
|
| 4.
|
Cole, S. T.,
Eiglmeier, K.,
Parkhill, J.,
James, X. D.,
Thomson, N. R.,
Wheeler, P. R.,
Honore, N.,
Garnier, T.,
Churcher, C.,
Harris, D.,
Mungall, K.,
Basham, D.,
Brown, D.,
Chillingworth, T.,
Connor, R.,
Davies, R. M.,
Devlin, X.,
Duthoy, S.,
Feltwell, T.,
Fraser, A.,
Hamlin, N.,
Holroyd, S.,
Hornsby, T.,
Jagels, K.,
Lacroix, C.,
Maclean, J.,
Moule, S.,
Murphy, L.,
Oliver, K.,
Quail, M. A.,
Rajandream, M.-A.,
Rutherford, K. M.,
Rutter, S.,
Seeger, K.,
Simon, S.,
Simmonds, M.,
Skelton, J.,
Squares, R.,
Squares, S.,
Stevens, K.,
Taylor, K.,
Whitehead, S.,
Woodward, J. R.,
and Barrell, B. G.
(2001)
Nature
409,
1007-1011
|
| 5.
|
Lecomte, J. T. J.,
Scott, N. L., Vu, B. C.,
and Falzone, C. J.
(2001)
Biochemistry
40,
6541-6552
|
| 6.
|
Das, T. K.,
Couture, M.,
Lee, H. C.,
Peisach, J.,
Rousseau, D. L.,
Wittenberg, B. A.,
Wittenberg, J. B.,
and Guertin, M.
(1999)
Biochemistry
38,
15360-15368
|
| 7.
|
Couture, M.,
Das, T. K.,
Savard, P. Y.,
Ouellet, Y.,
Wittenberg, J. B.,
Wittenberg, B. A.,
Rousseau, D. L.,
and Guertin, M.
(2000)
Eur. J. Biochem.
267,
4770-4780
|
| 8.
|
Scott, N. L.,
and LeComte, J. T. J.
(2000)
Protein Sci.
9,
587-597
|
| 9.
|
Hvitved, A. N.,
Trent, J. T., III,
Premer, S. A.,
and Hargrove, M. S.
(2001)
J. Biol. Chem.
276,
34714-34721
|
| 10.
|
Couture, M.,
Das, T. K.,
Lee, H. C.,
Peisach, J.,
Rousseau, D. L.,
Wittenberg, B. A.,
Wittenberg, J. B.,
and Guertin, M.
(1999)
J. Biol. Chem.
274,
6898-6910
|
| 11.
|
Das, T. K.,
Weber, R. E.,
Dewilde, S.,
Wittenberg, J. B.,
Wittenberg, B. A.,
Yamauchi, K.,
Van Hauwaert, M. L.,
Moens, L.,
and Rousseau, D. L.
(2000)
Biochemistry
39,
14330-14340
|
| 12.
|
Couture, M.,
Yeh, S-R.,
Wittenberg, B. A.,
Wittenberg, J. B.,
Ouellet, Y.,
Rousseau, D. L.,
and Guertin, M.
(1999)
Proc. Natl. Acad. Sci. U. S. A.
96,
11223-11228
|
| 13.
|
Watts, R. A.,
Hunt, P. W.,
Hvitved, A. N.,
Hargrove, M. S.,
Peacock, W. J.,
and Dennis, E. S.
(2001)
Proc. Natl. Acad. Sci. U. S. A.
98,
10119-10124
|
| 14.
|
Yeh, D. C.,
Thorsteinsson, M. V.,
Bevan, D. R.,
Potts, M.,
and La Mar, G. N.
(2000)
Biochemistry
39,
1389-1399
|
| 15.
|
Yeh, S. R.,
Couture, M.,
Ouellet, Y.,
Guertin, M.,
and Rousseau, D. L.
(2000)
J. Biol. Chem.
275,
1679-1684
|
| 16.
|
Bolognesi, M.,
Bordo, D.,
Rizzi, M.,
Tarricone, C.,
and Ascenzi, P.
(1997)
Prog.
Biophys. Mol. Biol.
68,
29-68
|
| 17.
|
Das, T. K.,
Couture, M.,
Ouellet, Y.,
Guertin, M.,
and Rousseau, D. L.
(2001)
Proc. Natl. Acad. Sci. U. S. A.
98,
479-484
|
| 18.
|
Yang, J.,
Kloek, A. P.,
Goldberg, D. E.,
and Matthews, F. S.
(1995)
Proc. Natl. Acad. Sci. U. S. A.
92,
4224-4228
|
| 19.
|
Peterson, E. S.,
Huang, S.,
Wang, J.,
Miller, L. M.,
Vidugiris, G.,
Kloek, A. P.,
Goldberg, D. E.,
Chance, M. R.,
Wittenberg, J. B.,
and Friedman, J. M.
(1997)
Biochemistry
36,
13110-13121
|
| 20.
|
Gibson, Q. H.,
and Smith, M. H.
(1965)
Proc. R. Soc. Lond. B Biol. Sci.
163,
206-214
|
| 21.
|
Das, T. K.,
Friedman, J. M.,
Kloek, A. P.,
Goldberg, D. E.,
and Rousseau, D. L.
(2000)
Biochemistry
39,
837-842
|
| 22.
|
Bolognesi, M.,
Cannillo, E.,
Ascenzi, P.,
Giacometti, G. M.,
Merli, A.,
and Brunori, M.
(1982)
J. Mol. Biol.
158,
305-315
|
| 23.
|
Scott, E. E.,
and Gibson, Q. H.
(1997)
Biochemistry
36,
11909-11917
|
| 24.
|
Das, T. K.,
Couture, M.,
Guertin, M.,
and Rousseau, D. L.
(2000)
J. Phys. Chem. B
104,
10750-10756
|
| 25.
|
Scott, E. E.,
Gibson, Q. H.,
and Olson, J. S.
(2001)
J. Biol. Chem.
276,
5177-5188
|
| 26.
|
Brunori, M.,
and Gibson, Q. H.
(2001)
EMBO Rep.
2,
674-679
|
| 27.
|
Frauenfelder, H.,
McMahon, B. H.,
Austin, R. H.,
Chu, K.,
and Groves, J. T.
(2001)
Proc. Natl. Acad. Sci. U. S. A.
98,
2370-2374
|
| 28.
|
Montet, Y.,
Amara, P.,
Volbeda, A.,
Vernede, X.,
Hatchikian, E. C.,
Field, M. J.,
Frey, M.,
and Fontecilla-Camps, J. C.
(1997)
Nat. Struct. Biol.
4,
523-526
|
| 29.
|
Whittington, D. A.,
Rosenzweig, A. C.,
Frederick, C. A.,
and Lippard, S. J.
(2001)
Biochemistry
40,
3476-3482
|
| 30.
|
Dobbek, H.,
Svetlitchnyi, V.,
Gremer, L.,
Huber, H.,
and Meyer, O.
(2001)
Science
293,
1281-1285
|
| 31.
|
Miles, E. W.,
Rhee, S.,
and Davies, D. R.
(1999)
J. Biol. Chem.
274,
12193-12196
|
| 32.
|
Couture, M.,
Chamberland, H., St.-,
Pierre, B.,
Lafontaine, J.,
and Guertin, M.
(1994)
Mol. Gen. Genet.
243,
185-197
|
| 33.
|
Hill, D. R.,
Belbin, T. J.,
Thorsteinsson, M. V.,
Bassam, D.,
Brass, S.,
Ernst, A.,
Boger, P.,
Paerl, H.,
Mulligan, M. E.,
and Potts, M.
(1996)
J. Bacteriol.
178,
6587-6598
|
| 34.
|
Thorsteinsson, M. V.,
Bevan, D. R.,
and Potts, M.
(1999)
Biochemistry
38,
2117-2126
|
| 35.
|
Wittenberg, J. B.
(1991)
in
Advances in Comparative and Environmental Physiology: Oxygen Carriers in Blood and Tissues
(Mangum, C. P., ed), Vol. 13
, pp. 59-85, Springer-Verlag New York Inc., New York
|
| 36.
|
Nathan, C.,
and Shiloh, M. U.
(2000)
Proc. Natl. Acad. Sci. U. S. A.
97,
8841-8848
|
| 37.
|
Eich, R. F., Li, T.,
Lemon, D. D.,
Doherty, D. H.,
Curry, S. R.,
Aitken, J. F.,
Mathews, A. J.,
Johnson, K. A.,
Smith, R. D.,
Phillips, G. N., Jr.,
and Olson, J. S.
(1996)
Biochemistry
35,
6976-6983
|
| 38.
|
Gardner, P. R.,
Gardner, A. M.,
Martin, L. A.,
and Salzman, A. L.
(1998)
Proc. Natl. Acad. Sci. U. S. A.
95,
10378-10383
|
| 39.
|
Herold, S.,
Exner, M.,
and Nauser, T.
(2001)
Biochemistry
40,
3385-3395
|
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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|
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278(7):
4919 - 4925.
[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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November 1, 2002;
277(45):
42540 - 42548.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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June 11, 2002;
99(12):
7992 - 7997.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Pathania, N. K. Navani, G. Rajamohan, and K. L. Dikshit
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277(18):
15293 - 15302.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide
PNAS,
April 30, 2002;
99(9):
5902 - 5907.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Ouellet, Y. Ouellet, C. Richard, M. Labarre, B. Wittenberg, J. Wittenberg, and M. Guertin
Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide
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April 30, 2002;
99(9):
5902 - 5907.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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