Lecture 16

Question 1

What does the graph in a simple ligand binding behavior?

Answer 1

A hyperbolic graph

Question 2

Which oxygen binding protein has a hyperbolic path?

Answer 2

Myoglobin

Question 3

What does the distal histidine do in Myoglobin?

Answer 3

Forms a hydrogen bonding relationship with the oxygen

Question 4

What coordination position does oxygen occupy?

Answer 4

The sixth coordination position

Question 5

Is binding reversible in myoglobin?

Answer 5

Yes

Question 6

Why is oxygen binding to myoglobin a reversible process?

Answer 6

Because we need the myoglobin to release the oxygen in certain conditions

Question 7

What is the percent of oxygen bound to myoglobin under active muscle conditions?

Answer 7

There is a low amount of oxygen bound because the partial pressure of oxygen is low

Question 8

What is the oxygen concentration bound to myoglobin at resting conditions?

Answer 8

It is significantly higher because PO2 is higher and lots of O2 is bound to the myoglobin

Question 9

What does the value of Kd in the oxygen binding to myoglobin curve represent?

Answer 9

When the concentration of the ligand is equal to Kd then we should expect half of our protein to be bound to the ligand and half of the protein to not be bound

Question 10

How does oxygen bind to myoglobin?

Answer 10

By forming an H-bond with the distal histidine

Question 11

How is the Heme prosthetic group held in the heme binding pocket?

Answer 11

By hydrophobic interactions

Question 12

What decreases carbon monoxide binding to myglobin?

Answer 12

The distal histidine

Question 13

What helps to define the geometry of the oxygen binding site?

Answer 13

The distal histidine

Question 14

What binds with higher affinity to myoglobin: Oxygen or Carbon Monoxide?

Answer 14

Carbon Monoxide

Question 15

What is the Quaternary Structure of Hemoglobin?

Answer 15

It is a Tetramer with two types of globin (two alpha and two beta subunits)

Question 16

What is the biggest thing the differentiates hemoglobin from myoglobin?

Answer 16

Hemoglobin has quaternary structure and isn’t just a single polypeptide. Because hemoglobin has four polypeptides

Question 17

What is each polypeptide in hemoglobin associated with?

Answer 17

A heme prosthetic group

Question 18

Which one of the oxygen carrying proteins is heterotetrameric?

Answer 18

Hemoglobin because it has four subunits and they are different from each other

Question 19

Which type of structure is the same for alpha globin, beta globin and myoglobin?

Answer 19

Tertiary structure

Question 20

What do the Alpha globin, beta globin and myoglobin all have in common?

Answer 20

They have 8 alpha helicases with a heme binding pocket between helices E and F

Question 21

What are Homologous proteins?

Answer 21

Proteins that are descendant from a common ancestor

Question 22

How many O2 can hemoglobin bind to?

Answer 22

4 O2 groups

Question 23

What kind of protein is Myoglobin?

Answer 23

A monomeric protein

Question 24

What is a conservative amino acid substitution?

Answer 24

When one amino acid is changed into one that is quite similar

Question 25

How does Conservative substitution affect structure and function?

Answer 25

It typically has relatively minor effects on structure/function

Question 26

What is a critical amino acid substitution?

Answer 26

When one amino acid is changed into one that is quite different

Question 27

How does Critical substitution affect structure and function?

Answer 27

They change the structure and function depending on location

Question 28

How do the alpha and beta subunit of hemoglobin vs myoglobin bind O2?

Answer 28

In the exactly same manner

Question 29

What critical residues near the oxygen binding sites are invariant (do not change)?

Answer 29

``` His F8 (proximal histidine) His E7 (distal histidine) ```

Question 30

What does a Hyperbolic curve indicate?

Answer 30

A hyperbolic curve indicates a constant affinity

Question 31

What does a Sigmoidal curve indicate?

Answer 31

Cooperative binding affinity

Question 32

What is Ligand affinity like in a hyperbolic curve?

Answer 32

The ligand affinity does not change

Question 33

What is Ligand affinity like in a sigmoidal curve?

Answer 33

Ligand affinity changes as more ligand binds

Question 34

What has a hyperbolic binding curve and what has a sigmoidal binding curve?

Answer 34

Hyperbolic - Myoglobin | Sigmoidal - Hemoglobin

Question 35

What is the Proximal Histidine important for?

Answer 35

Iron atom coordination and maintaining the oxidation state

Question 36

What is the distal histidine involved in?

Answer 36

The H-bonding interaction of the oxygen

Question 37

What does the sigmoidal curve in hemoglobin indicate?

Answer 37

Positive cooperativity

Question 38

Aside from hemoglobin where can positive cooperativity be seen?

Answer 38

In the denaturation of DNA, where it is difficult to begin denaturation but easy to continue

Question 39

When does Myoglobin bind oxygen?

Answer 39

When the tissues are in resting state and the oxygen concentration is very high

Question 40

When does Myoglobin release oxygen?

Answer 40

When the tissue is relatively active

Question 41

Where does Hemoglobin transport oxygen from and to?

Answer 41

From the lungs to the peripheral tissues

Question 42

When does oxygen bind to hemoglobin and release it?

Answer 42

Hemoglobin binds to oxygen in the lungs where concentration is relatively high and lets go in the tissue

Question 43

Why doesn't the body exclusively use myoglobin?

Answer 43

Because myoglobin will happily bind to oxygen in the lungs but as it circulates through the body and gets to the peripheral tissues it won't let go of the oxygen

Question 44

Which has a higher affinity for oxygen: Myoglobin or Hemoglobin?

Answer 44

Myoglobin

Question 45

What are the similar functions of Myoglobin Hemoglobin?

Answer 45

They reversibly bind/release O2

Question 46

What are the different function of Myoglobin and Hemoglobin?

Answer 46

Mb: O2 transport within tissue Hb: O2 transport from lungs to tissues

Question 47

What are the two states of Hb?

Answer 47

Tense (T) state and Relaxed (R) state

Question 48

What is the Tense (T) state of hemoglobin?

Answer 48

The low oxygen affinity state

Question 49

What is the Relaxed (R) state of hemoglobin?

Answer 49

The high affinity state

Question 50

What is the Tense state associated with?

Answer 50

A higher amount of salt bridge/ion pair interactions

Question 51

What is the difference between the subunits in the tense state and relaxed state?

Answer 51

There is a change in how the subunits are interacting with each other. Changing the shape of one subunit changes the shape of another subunit

Question 52

What is the size of the central cavity in the tense state versus the relaxed state?

Answer 52

The tense state has a larger central cavity and the relaxed state has smaller central cavity

Question 53

What are Effectors?

Answer 53

Compounds which, upon binding, alter affinity at other binding sites

Question 54

What is a Homoallosteric effector?

Answer 54

When the binding of the effector effects further binding of the same compound

Question 55

What is Allostery generally associated with?

Answer 55

Proteins with quaternary structure

Question 56

What is a Heteroallosteric Effector?

Answer 56

When the binding of the effector effects further binding of a different compound

Question 57

What do Activators (positive effectors) do?

Answer 57

Increase binding affinity

Question 58

What do Inhibitors (negative effectors) do?

Answer 58

Decrease binding affinity

Question 59

What kind of effector is oxygen to hemoglobin?

Answer 59

A homoallosteric positive effector