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* Residue conservation analysis
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Enzyme class:
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Chains A, B, C, D:
E.C.?
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DOI no:
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Biochemistry
44:8347-8359
(2005)
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PubMed id:
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The enigma of the liganded hemoglobin end state: a novel quaternary structure of human carbonmonoxy hemoglobin.
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M.K.Safo,
D.J.Abraham.
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ABSTRACT
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The liganded hemoglobin (Hb) high-salt crystallization condition described by
Max Perutz has generated three different crystals of human adult carbonmonoxy
hemoglobin (COHbA). The first crystal is isomorphous with the "classical"
liganded or R Hb structure. The second crystal reveals a new liganded Hb
quaternary structure, RR2, that assumes an intermediate conformation between the
R form and another liganded Hb quaternary structure, R2, which was discovered
more than a decade ago. Like the R2 structure, the diagnostic R state hydrogen
bond between beta2His97 and alpha1Thr38 is missing in the RR2 structure. The
third crystal adopts a novel liganded Hb conformation, which we have termed R3,
and it shows substantial quaternary structural differences from the R, RR2, and
R2 structures. The quaternary structure differences between T and R3 are as
large as those between T and R2; however, the T --> R3 and T --> R2
transitions are in different directions as defined by rigid-body screw rotation.
Moreover, R3 represents an end state. Compared to all known liganded Hb
structures, R3 shows remarkably reduced strain at the alpha-heme, reduced steric
contact between the beta-heme ligand and the distal residues, smaller alpha- and
beta-clefts, and reduced alpha1-alpha2 and beta1-beta2 iron-iron distances.
Together, these unique structural features in R3 should make it the most relaxed
and/or greatly enhance its affinity for oxygen compared to the other liganded
Hbs. The current Hb structure-function relationships that are now based on T
--> R, T -->R --> R2, or T --> R2 --> R transitions may have to
be reexamined to take into account the RR2 and R3 liganded structures.
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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.S.Hub,
M.B.Kubitzki,
and
B.L.de Groot
(2010).
Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation.
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PLoS Comput Biol,
6,
e1000774.
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M.Balasubramanian,
P.S.Moorthy,
K.Neelagandan,
and
M.N.Ponnuswamy
(2009).
Purification, crystallization and preliminary crystallographic study of low oxygen-affinity haemoglobin from cat (Felis silvestris catus) in two different crystal forms.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
65,
313-316.
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D.H.Maillett,
V.Simplaceanu,
T.J.Shen,
N.T.Ho,
J.S.Olson,
and
C.Ho
(2008).
Interfacial and distal-heme pocket mutations exhibit additive effects on the structure and function of hemoglobin.
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Biochemistry,
47,
10551-10563.
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M.Cammarata,
M.Levantino,
F.Schotte,
P.A.Anfinrud,
F.Ewald,
J.Choi,
A.Cupane,
M.Wulff,
and
H.Ihee
(2008).
Tracking the structural dynamics of proteins in solution using time-resolved wide-angle X-ray scattering.
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Nat Methods,
5,
881-886.
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P.Cozzini,
G.E.Kellogg,
F.Spyrakis,
D.J.Abraham,
G.Costantino,
A.Emerson,
F.Fanelli,
H.Gohlke,
L.A.Kuhn,
G.M.Morris,
M.Orozco,
T.A.Pertinhez,
M.Rizzi,
and
C.A.Sotriffer
(2008).
Target flexibility: an emerging consideration in drug discovery and design.
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J Med Chem,
51,
6237-6255.
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P.S.Kaushal,
R.Sankaranarayanan,
and
M.Vijayan
(2008).
Water-mediated variability in the structure of relaxed-state haemoglobin.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
463-469.
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PDB codes:
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T.Yonetani,
and
M.Laberge
(2008).
Protein dynamics explain the allosteric behaviors of hemoglobin.
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Biochim Biophys Acta,
1784,
1146-1158.
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X.J.Song,
V.Simplaceanu,
N.T.Ho,
and
C.Ho
(2008).
Effector-induced structural fluctuation regulates the ligand affinity of an allosteric protein: binding of inositol hexaphosphate has distinct dynamic consequences for the T and R states of hemoglobin.
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Biochemistry,
47,
4907-4915.
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K.Neelagandan,
P.S.Moorthy,
M.Balasubramanian,
and
M.N.Ponnuswamy
(2007).
Crystallization of sheep (Ovis aries) and goat (Capra hircus) haemoglobins under unbuffered low-salt conditions.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
63,
887-889.
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S.C.Sahu,
V.Simplaceanu,
Q.Gong,
N.T.Ho,
F.Tian,
J.H.Prestegard,
and
C.Ho
(2007).
Insights into the solution structure of human deoxyhemoglobin in the absence and presence of an allosteric effector.
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Biochemistry,
46,
9973-9980.
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X.J.Song,
Y.Yuan,
V.Simplaceanu,
S.C.Sahu,
N.T.Ho,
and
C.Ho
(2007).
A comparative NMR study of the polypeptide backbone dynamics of hemoglobin in the deoxy and carbonmonoxy forms.
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Biochemistry,
46,
6795-6803.
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L.Ronda,
S.Bruno,
C.Viappiani,
S.Abbruzzetti,
A.Mozzarelli,
K.C.Lowe,
and
S.Bettati
(2006).
Circular dichroism spectroscopy of tertiary and quaternary conformations of human hemoglobin entrapped in wet silica gels.
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Protein Sci,
15,
1961-1967.
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S.V.Lepeshkevich,
and
B.M.Dzhagarov
(2005).
Mutual effects of proton and sodium chloride on oxygenation of liganded human hemoglobin.
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FEBS J,
272,
6109-6119.
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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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Links
