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PDBsum entry 1qsi
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Oxygen storage/transport
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PDB id
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1qsi
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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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Magnesium(ii) and zinc(ii)-Protoporphyrin IX'S stabilize the lowest oxygen affinity state of human hemoglobin even more strongly than deoxyheme.
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Authors
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G.Miyazaki,
H.Morimoto,
K.M.Yun,
S.Y.Park,
A.Nakagawa,
H.Minagawa,
N.Shibayama.
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Ref.
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J Mol Biol, 1999,
292,
1121-1136.
[DOI no: ]
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PubMed id
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Abstract
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Studies of oxygen equilibrium properties of Mg(II)-Fe(II) and Zn(II)-Fe(II)
hybrid hemoglobins (i.e. alpha2(Fe)beta2(M) and alpha2(M)beta2(Fe); M=Mg(II),
Zn(II) (neither of these closed-shell metal ions binds oxygen or carbon
monoxide)) are reported along with the X-ray crystal structures of
alpha2(Fe)beta2(Mg) with and without CO bound. We found that Mg(II)-Fe(II)
hybrids resemble Zn(II)-Fe(II) hybrids very closely in oxygen equilibrium
properties. The Fe(II)-subunits in these hybrids bind oxygen with very low
affinities, and the effect of allosteric effectors, such as proton and/or
inositol hexaphosphate, is relatively small. We also found a striking similarity
in spectrophotometric properties between Mg(II)-Fe(II) and Zn(II)-Fe(II)
hybrids, particularly, the large spectral changes that occur specifically in the
metal-containing beta subunits upon the R-T transition of the hybrids. In
crystals, both alpha2(Fe)beta2(Mg) and alpha2(Fe-CO)beta2(Mg) adopt the
quaternary structure of deoxyhemoglobin. These results, combined with the
re-evaluation of the oxygen equilibrium properties of normal hemoglobin,
low-affinity mutants, and metal substituted hybrids, point to a general tendency
of human hemoglobin that when the association equilibrium constant of hemoglobin
for the first binding oxygen molecule (K1) approaches 0.004 mmHg(-1), the
cooperativity as well as the effect of allosteric effectors is virtually
abolished. This is indicative of the existence of a distinct thermodynamic state
which determines the lowest oxygen affinity of human hemoglobin. Moreover,
excellent agreement between the reported oxygen affinity of deoxyhemoglobin in
crystals and the lowest affinity in solution leads us to propose that the
classical T structure of deoxyhemoglobin in the crystals represents the lowest
affinity state in solution.We also survey the oxygen equilibrium properties of
various metal-substituted hybrid hemoglobins studied over the past 20 years in
our laboratory. The bulk of these data are consistent with the Perutz's trigger
mechanism, in that the affinity of a metal hybrid is determined by the ionic
radius of the metal, and also by the steric effect of the distal ligand, if
present. However, there remains a fundamental contradiction among the oxygen
equilibrium properties of the beta substituted hybrid hemoglobins.
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Figure 5.
Figure 5. pH dependence of K[1]at 25°C for Hb A (0m)
and low-affinity hybrid Hbs, (a) a[2](Fe)b[2](M) and (b)
a[2](M)b[2](Fe); M = Mg(II) (  diamond
), Zn(II) (  up
triangle, open ), Ni(II) (  open
), Cu(II) (  triangle,
open ), and PP (  star,
filled, low ). The filled symbols indicate the presence of 2 mM
IHP. The protein concentration was about 60 µM (on a metal
ion basis) except for that of Ni-Fe hybrids (16 µM). An
arrow indicates the oxygen affinity of Hb A in crystals at
25°C. The sources of the data are described in Table 2.
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Figure 6.
Figure 6. Stereoscopic comparison of the vicinity of the a1
heme between a[2](Fe-CO)b[2](Mg) (filled bonds) and
a[2](Fe)b[2](Mg) (open bonds). The iron, four pyrrole rings, and
four methine carbon atoms are superimposed.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
292,
1121-1136)
copyright 1999.
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Secondary reference #1
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Title
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High-Resolution crystal structure of magnesium (mgii)-Iron (feii) hybrid hemoglobin with liganded beta subunits.
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Authors
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S.Y.Park,
A.Nakagawa,
H.Morimoto.
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Ref.
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J Mol Biol, 1996,
255,
726-734.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. Fragment difference electron density map of
b2 heme in a(
Mg(II)
)2b(
Fe(II)-CO
)2 , based on 1.9 Å resolution
data of =2Fo - Fc=. The electron density map was contoured
at 1.5 standard deviations above the average density of the
map. The Fe atom was at the heme center. The
comparatively small temperature factor of bound CO
molecules (C = 19 Å 2
, O = 20 Å 2
) suggests that they had
an occupancy close to 100%. The map for b1 heme was
similar.
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Figure 5.
Figure 5. A comparison of the b1 heme and b E11 Val
of the a(
Mg(II)
)2 b(
Fe(II)-CO
)2 (green bonds), deoxy HbA
(yellow bonds) and COHbA (blue bonds) together with
those of a(
Ni(II)
)2 b(
Fe(II)-CO
)2 (red bonds) is shown in the
BGH frame of the a1b1 interface. The r.m.s. differences
between the b1 heme positions (porphyrin nitrogen and
carbon atoms plus the first 32 side-chain atoms) of
a(
Ni(II)
)2b(
Fe(II)-CO
)2 , a(
Mg(II)
)2b(
Fe(II)-CO
)2 , COHbA and deoxy
HbA (PEG) in the BGH frame of the a1b1 interface, are
0.33 Å , 0.40 Å and 1.40 Å , respectively. The coordinates
other than the first one were taken from the Brookhaven
data base.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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