The heme group. The visible absorption spectra of oxygenated and deoxygenated hemoglobins. Oxygen dissociation curves of Mb and of Hb in whole blood. Hill plots for Mb and purified (“stripped”) Hb.
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Hb(O2)nHx + O2 Hb(O2)n+1 + xH+
x ≈ 0.6
catalyzed by carbonic anhydrase in erythrocytes
Carbamate Formation (N-termini)
R-NH2 + CO2R-NH-COO- + H+
DeoxyHb binds more CO2 as carbamate
than does oxyHb
affinityComparison of the O2-dissociation curves of “stripped” Hb and whole blood in 0.01M NaCl at pH 7.0.
The effects of 2,3-BPG and CO2, both separately and combined, on hemoglobin’s O2-dissociation curve compared with that of whole blood (red curve).
of a and b subunits
are similar to each
other and to Mb
There is extensive
(a1-b1 and a2-b2); hydrophobic
Contacts between like
subunits few and polarThe X-ray structure of deoxyHb as viewed down its exact 2-fold axes.
structural changes occur
to Hb upon oxgenation
Changes occur at the
a1-b2 and a2-b1 interfacesThe X-ray structure of oxyHb as viewed down its exact 2-fold axes.
thea1-b1 dimer by 15o with
respect to the a2-b2dimer;
deoxyHb = Tstate (tense)
oxyHb = Rstate (relaxed)The major structural differences between the quaternary conformations of (a) deoxyHb and (b) oxyHb
(based on X-ray analyses)
Fe(II) in deoxyHb;
ion moves in-plane in
oxyHb, and pulls
on the proximal
His; F helix is movedThe heme group and its environment in the unliganded a chain of human Hb.
states are allowed:
a binary switchThe a1C–b2FG interface of Hb in (a) the T state and (b) the R state.
blue: oxyHbThe hemoglobin a1b2 interface as viewed perpendicularly to Fig. 10-13.
must break in T to
Val-1 on a2:
Bohr effectNetworks of salt bridges and hydrogen bonds in deoxyHb. (a) Last two residues of the a chains.
Bohr effectNetworks of salt bridges and hydrogen bonds in deoxyHb. (b) Last two residues of the b chains.
T and R states vary with
Overall binding curve for Hb
is a composite of the hyperbolic
binding curves for pure T and RFree energy and saturation curves for O2 binding to hemoglobin
groups) lacks 20-30% of the Bohr effect.Reaction of cyanate with the unprotonated (nucleophilic) forms of primary amino groups.
with positive charge
(Lys, His, N-termini):
complementary to BPG’s
binds to deoxyHb: central
cavity is smaller in oxyHbBinding of BPG to deoxyHb: selective stabilization of the T form
860 variant Hbs in humans
Mutations stabilizing the Fe(III) oxidation state of heme. (a) Alterations in the heme pocket of the a subunit on changing from deoxyHbA to Hb Boston.
Glu A3(6)bElectron micrograph of deoxyHbS fibers spilling out of a ruptured erythrocyte.
Val 6 involving b2;
Val 6 of b1 - pocketStructure of the deoxyHbS fiber: a schematic diagram indicating the intermolecular contacts in the crystal structure of deoxyHbS.
Structure of the deoxyHbS fiber: the mutant Val 6b2 fits neatly into a hydrophobic pocket formed mainly by Phe 85 and Leu 88 of an adjacent b1 subunit.
1/td = k(ct/cs)n: concentration dependence of the delay timeTime course of deoxyHbS gelation: the extent of gelation as monitored calorimetrically (yellow) and optically (purple).
concentration dependenceTime course of deoxyHbS gelation: a log–log plot showing the concentration dependence of 1/tdfor the gelation of deoxyHbS at 30°C.
two general models
Monod, Wyman, Changeux:
conformational change alters
affinity for ligand: molecular
symmetry conservedThe species and reactions permitted under the symmetry model of allosterism
intermediate conformationsSequential binding of ligand in the sequential model of allosterism
model of Hb
Free energy penalties for binding O2 to various ligation states of Hb tetramers relative to O2-binding to noncooperative Hb ab dimers.