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