Protein Dynamics Hemoglobin Structure and Function
shatter
When deoxy-Hb crystals are exposed to oxygen, they ______________. Evidence of a large-scale structural change
porphyrin
When oxygen binds to Fe in heme of Mb, the heme Fe is drawn toward the plane of the ____________ ring
central cavity (of Hb)
Where does 2,3-BPG bind?
closer
Upon O2 binding, the Fe2+ atom moves about 0.039 nm _________ to the plane of the heme, drawing iron into the plane
2,3-BPG
What interacts with amino acid side chains of both beta-globin chains: Lys beta-82, His beta-2, His beta-143, and the amino terminus?
sixth
When Mb or Hb bind oxygen, the O2 molecule adds to the heme iron as the ________ ligand
Because it has a Lower Affinity for BPG
Why does Fetal Hemoglobin Has a Higher Affinity for O2?
out
Without oxygen bound, Fe2+ is ______ of heme plane
95, 85, 70
_____% of cytosolic protein in RBC is hemoglobin ____% of total body heme is in RBC ___% of total body iron is in RBC
CO2
______ Also Promotes the Dissociation of O2 from Hemoglobin
Cl-
______ ion also stabilizes deoxy Hb.
Hemoglobin, myoglobin
____________ and _________________ are oxygen transport and storage proteins
Deoxy Hb
______________ binds CO2 in tissues, transports it to the lungs, and releases it.
Electronegative, positive
_________________ 2,3-BPG binds to ____________ charged functional groups of the beta globin chains in the central cleft of the Hb tetramer.
Cooperative
__________________ Binding of Oxygen Influences Hemoglobin Function
hydrophobic, deoxygenated
valine binds to _____________ pocket, forming an aggregate and distort shape of RBC in Sickle Cell Anemia (only when Hb is _________________)
True
(T/F): myoglobin always has higher saturation of oxygen than hemoglobin
True
(T/F): nucleus condenses upon maturation in erythroid development
myoglobin
153 aa, 17,200 MW
electronegative
2,3-BPG is very ___________________
2,3-BPG (2,3-Bisphosphoglycerate)
An Allosteric Effector of Hemoglobin
Bohr Effect
Antagonism of O2 Binding by H+ is Termed the ___________________
higher
As a result, fetal Hb has a ___________ affinity for O2
promoting
At the lung-artery interface, bicarbonate dehydration (required for CO2 exhalation) consumes extra H+, _________________ O2 binding
dissociation
At the tissue-capillary interface, CO2 hydration and glycolysis produce extra H+, promoting additional _________________ of O2 where it is needed most
Physiological
BPG Binding to Hb Has Important _________ Significance
less, left
BPG binds _______ tightly to deoxy-HbF; so HbF has a higher affinity for oxygen (O2 binding curve shifted to _________)
H+, CO2, chloride ions
Binding of O2 to Hb is affected by several agents, including...
proton
Binding of oxygen diminishes _____________ binding
oxygen
Binding of protons diminishes __________ binding
higher
Deoxy-Hb has a ___________ affinity for H+ than oxy-Hb
diminishes
Carbon dioxide _______________ oxygen binding
conformational changes
Changes in the position of the heme iron atom upon oxygenation lead to ____________________ in the hemoglobin molecule.
0.04
Fe2+ Movement by Less Than _____ nm Induces the Conformation Change in Hb
F8
Fe2+ is coordinated by His _______
F8
Fe2+ pulls its His ___ ligand along with it
gamma
Fetal Hb differs from adult Hb, with _______________-chains in place of beta-chains - and thus a alpha-2-gamma-2 structure
Ser, two
Fetal gamma-chains have ______ instead of His at position 143 and thus lack ______ of the positive charges in the BPG binding cavity
proton
Hydration of CO2 in tissues and extremities leads to ___________ production. These ___________ are taken up by Hb as oxygen dissociates
100
Hb becomes saturated with O2 in the lungs, where the partial pressure of O2 is about ______ torr
lungs, capillaries
Hb must be able to bind oxygen in the _______, and release oxygen in the _____________
protoporphyrin IX
Heme is formed when _______________ binds Fe2+
increases
Hemoglobin content __________ with erythroid differentiation (as RBC matures)
tetrameric
Hemoglobin is _____________
tetrameric
Hemoglobin is a ___________ protein
allosteric
Hemoglobin is a classic example of _______________ regulation
beta
In Sickle Cell Anemia, there is a single nucleotide change in the ________-globin gene
deoxy-Hb
In ___________, the iron atom lies out of the heme plane by about 0.06 nm
deoxymyoglobin
In __________________, the ferrous ion actually lies 0.055 nm above the plane of the heme
40
In capillaries, pO2 is about ____ torr, and oxygen is released from Hb
rectangular hyperbola
In the absence of 2,3-BPG, oxygen binding to Hb follows a ______________________
Bohr Effect
Increased [H+] Shifts O2 Binding Curve to the Right
6
Iron interacts with ____ ligands in Hb and Mb
imidazole
Iron interacts with six ligands in Hb and Mb and 4 of these are the N atoms of the porphyrin. A fifth ligand is donated by the _____ side chain of amino acid residue His F8
N atoms
Iron interacts with six ligands in Hb and Mb and 4 of these are the _________ of the porphyrin
porphryins
Mb and Hb use ____________ to bind Fe2+
heme
Mb is a monomeric ________ protein
E, F
Mb polypeptide "cradles" the heme group between ___ and ____
metmyoglobin
Mb with Fe3+ is called _________________ and does not bind oxygen
greater
Mb, an oxygen storage protein, has a _____________ affinity for oxygen at all oxygen pressures
monomeric
Myoglobin is ____________
S-nitroso
NO reacts with the -SH of Cys93β, forming an _____________ derivative, protecting iron from binding NO and hemoglobin can bind Oxygen
beta
Negative charges of 2,3-BPG interact with 2 Lys, 4 His, 2 N-termini of the _________-globin subunits
Myoglobin
O2 Binding Alters ________ Conformation
15, oxygen
One alpha-beta pair moves relative to the other by _____ degrees upon ______________ binding. This massive change is induced by movement of Fe by 0.039 nm when oxygen binds
ferric iron (Fe 3+)
Oxidation of Fe yields _______________
Quaternary
Oxygen Binding by Hb Induces a _____________ Structure Change
binding
Oxygen ____________ pulls the Fe2+ into the heme plane
50
P50 is the partial pressure of oxygen at which Hb is ___% saturated.
H+
Promotes Dissociation of Oxygen from Hb
Hemoglobin
Red Blood Cells Contain ______________
alpha/beta thalassemia
Reduced levels of alpha/beta
F
The ___ helix moves when oxygen binds
sigmoid, cooperative
The __________, _______________ oxygen binding curve of Hb makes its physiological actions possible
sigmoid
The _______________ binding curve is only observed in the presence of 2,3-BPG
allosteric effector
Since 2,3-BPG binds at a site distant from the Fe where oxygen binds, it is called an ___________________
Sickle Cell Anemia
Single nucleotide change in the beta-globin gene that results in a single amino acid change (Glu to Val - Val is hydrphobic) that causes disease
perpendicular
The O2 molecule is tilted ___________________ relative to the heme plane
inversely
The P50 is ____________ proportional to the oxygen affinity.
equilibrium, thiols
The S-nitroso group is in ____________ with other S-nitroso compounds formed by reaction of nitric oxide with small-molecule ________ such as free Cys or glutathione
independent, placenta
The fetus depends on its mother for O2, but its circulatory system is entirely ______________. Gas exchange takes place across the ________________.
cooperative, more
The binding of O2 to Hb is _______________ - binding of oxygen to the first subunit makes binding to the other subunits _______ favorable
monomer
The structure of myoglobin is similar to that of the hemoglobin ___________
allosteric
The structure, in ionic form of BPG or 2,3-bisphosphoglycerate, an important ____________ effector of Hb
Nitric oxide (NO)
a high-affinity ligand for Hb, binding to the heme iron 10,000 times more tightly than O2
adjacent
a similar (to Mb) change in Hb initiates a series of conformational changes that are transmitted to ________________ subunits
Nitric oxide (NO)
a simple gaseous molecule that acts as a neurotransmitter and as a second messenger in signal transduction
decreases
as pH ____________, dissociation of O2 from hemoglobin is enhanced
sickle cell anemia
caused by single mutation in beta globin
Cooley's Anemia
caused by the absence of beta globin chains
salt bridges
conformational change in Hb leads to a rupture of _______________
sigmoidal, rectangular hyperbole (saturates quickly)
hemoglobin curve is what shape? myoglobin curve is what shape?
Fetal Hb
lower affinity for 2,3-BPG, higher affinity for oxygen, so it can get oxygen from mother
hemoglobin
must bind oxygen in lungs and release it in capillaries
conformational change
oxygen binding causes......
sigmoid
oxygen binding curve for hemoglobin is what shape?
2,3-BPG
stabilizes deoxy Hb inside red blood cells
R (relaxed) state (OxyHb)
the form of hemoglobin that has a higher affinity to oxygen.
T (tense) state (Deoxy-Hb)
the form of hemoglobin that has a lower affinity to oxygen.
Ferrous iron (Fe 2+)
the iron form that binds oxygen in myoglobin
positive cooperation
the sigmoid shape curve is due to...
small-molecule thiols
transfer NO from erythrocytes to endothelial receptors, where it exerts its physiological effects
hemoglobin
two α chains of 141 residues, 2 β chains of 146 residues