Structures and Function Receptors and Ligands

Question 1

Small molecules that binds a protein at a binding site

Answer 1

Ligands

Question 2

Binds at the binding site and results in a response. Not a normal ligand. Ex: Opiates binding in the place of normal endorphins

Answer 2

Agonist

Question 3

Something that binds and block the binding site

Answer 3

Antagonist

Question 4

Proteins bind ligand by slightly _ their _

Answer 4

adjusting, conformations

Question 5

Why must ligand binding be a reversible process?

Answer 5

The receptors need to be reused

Question 6

O2 binding to myoglobin and hemoglobin. ATP binding to myosin. Actin binding

Answer 6

Protein-ligand interaction examples

Question 7

With protein and ligand binding, when there is a high concentration of ligand there is more of what form

Answer 7

More of the complex state (PL)

Question 8

The dissociation constant measures what?

Answer 8

Kd measures binding affinity

Question 9

when kd = [L] what is theta

Answer 9

1/2. Kd is the [L] where 1/2 of the binding sites are occupied

Question 10

Smaller Kd is weaker or stronger affinity for the ligand?

Answer 10

Stronger

Question 11

A monomeric protein in the Globin family. Hemoglobin has 4 of these

Answer 11

Myoglobin (Mb)

Question 12

Myoglobin is what kind of storehouse?

Answer 12

O2 storehouse. Binds and releases oxygen

Question 13

Structural adaptation that occurs between protein and ligand

Answer 13

induced fit

Question 14

Why do we need a delivery system for a gas like oxygen?

Answer 14

Oxygen is not very soluble in liquid and water. Needs to be bound to something like myoglobin

Question 15

Myoglobin’s center contains iron. Why is that important?

Answer 15

Fe and Cu have a strong tendency to bind to O2. They reversibly bind to O2.

Question 16

Iron is often incorporated into a protein bound prosthetic group called _

Answer 16

heme

Question 17

Iron atom has 6 coordinated bonds, 4 nitrogen atoms that are part of a flat _ ring system. Nitrogens are a part of histidines

Answer 17

Porphyrin

Question 18

Can any amino acids reversibly bind to O2

Answer 18

No

Question 19

What does heme do when it is coordinated with a protein?

Answer 19

It controls the reactivity of the Fe (Iron)

Question 20

Histidine coordinates the Fe and allows how many sides of Fe to bind to O2?

Answer 20

One

Question 21

The specific structure of the binding pocket will affect…

Answer 21

ligand binding

Question 22

Myoglobin slightly “breathes” between what states

Answer 22

bound and unbound

Question 23

CO and NO bind with a higher affinity to the heme iron than O2. Why is that bad?

Answer 23

When CO or NO bind to the heme group, oxygen is excluded and cannot be transported through the body.

Question 24

Mb follows what kind of binding pattern

Answer 24

hyperbolic

Question 25

Carries O2 from lungs to tissues. 4 subunits (2 alpha + 2 beta, each with one Heme Fe). Subunits are similar to Mb

Answer 25

Hemoglobin (Hb)

Question 26

What forces hold the hemoglobin subunits together?

Answer 26

Hydrogen bonds, hydrophobic interactions, covalent, ionic, and van der Waals.

Question 27

Hb subunits change conformation slightly when O2 is bound. What are the two conformations?

Answer 27

T state and R state

Question 28

Which conformation has a low affinity to oxygen?

Answer 28

T state

Question 29

Which conformation has a high affinity to oxygen?

Answer 29

R state

Question 30

The transition from T state to R state is called what?

Answer 30

Cooperative Binding

Question 31

Where the binding of one ligand affects the structure and the binding affinity of the other ligand

Answer 31

Cooperative binding

Question 32

Cooperative binding of T and R states allows what to occur?

Answer 32

Allows Hb to pick up and deliver its cargo

Question 33

Sigmoid binding curves suggest what kind of binding?

Answer 33

Cooperative binding

Question 34

What do sigmoid binding curves show?

Answer 34

The transition from low to high-affinity conformation

Question 35

Sigmoid curves are an example of allostery. What does that mean?

Answer 35

Binding at one site affects the shape of another site

Question 36

What 4 things contribute to the binding affinity of O2 in Hb (thus the stabilization of the R and T states)?

Answer 36

pO2 (how much O2 is around), pH, CO2 concentration, and binding of 2,3-Bishosphoglycerate (BPG)

Question 37

Which state occurs when the histidine residues are in the center of hemoglobin?

Answer 37

The R state. Histidine's are deprotonated and neutral, so they can be next to each other

Question 38

What part of the body is the R state commonly found?

Answer 38

The lungs

Question 39

Which state is associated with a high pH (more basic)?

Answer 39

The R state

Question 40

Which state is associated with a low pH (more acidic)?

Answer 40

The T state

Question 41

Which part of the body is the T state commonly found?

Answer 41

The muscles

Question 42

In the T state, the histidine residues are on opposite sides of hemoglobin. Why?

Answer 42

Because the T state has a lower pH, the histidine residues are protonated and charged. When they are next to each other, they repel each other so they have to be farther away.

Question 43

In the T state, what other amino acid do the histidine residues have electrostatic interactions with?

Answer 43

Asp

Question 44

Step 1 of Hb process

Answer 44

In lungs, pO2 is high, CO2 is low, and pH of blood is about 7.6. Hb arrives in T state with no O2 and with BPG bound.

Question 45

Step 2 of Hb process

Answer 45

Hb recognizes that there is oxygen to deliver. BPG unbinds so that oxygen can bind

Question 46

Step 3 of Hb process

Answer 46

Because the first O2 molecules bound, the other O2 molecules binding is easy. There is cooperative binding so a transition into the R state occurs.

Question 47

Step 4 of Hb process

Answer 47

Heme group is taken to the muscle tissue. A working muscle needs O2. The pO2 is low, the CO2 is high, and the pH is about 7.2 (lower than before)

Question 48

Step 5 of Hb process

Answer 48

H+ binds to specific residues on Hb (Ex: HisHc3) which causes Hb to return to the T state. O2 falls off Hb to participate in cellular respiration

Question 49

Why is the pH lower in deep tissues?

Answer 49

Enzyme carbonic anhydrase turns CO2 into bicarbonate, which diffuses out in the blood and lowers pH. Indirect effect of CO2 on the T-state

Question 50

Step 6 of Hb process

Answer 50

CO2 binds to the N-term of each globin chain which stabilizes the T state. H+ binds to other amino acids (like HisHc3 which binds to Asp94)

Question 51

How many carbon dioxides can each hemoglobin pick up and take to blood

Answer 51

4

Question 52

H+ and CO2 binding to different sites on the Hb _ the T-state. This is a _ effect

Answer 52

Stabilizes, Direct

Question 53

Step 7 of Hb process

Answer 53

BPG returns and binds to Hb which further stabilizes the T-state. Makes sure that the O2 stays out

Question 54

When is BPG produced?

Answer 54

During regular metabolism

Question 55

How many BPG molecules binds the Hb tetramer between the beta subunits in the T-state?

Answer 55

1

Question 56

What is predominate charge on BPG?

Answer 56

Negative

Question 57

What kind of amino acids are responsible for BPG binding to the beta subunits?

Answer 57

Positively charged amino acids like Lysine, Arginine, Histidine

Question 58

At high concentrations, should BPG be bound or unbound?

Answer 58

Bound

Question 59

Bohr effect for hemoglobin

Answer 59

The Bohr effect describes hemoglobin’s lower affinity for oxygen secondary to increases in the partial pressure of carbon dioxide and/or decreased blood pH. This lower affinity, in turn, enhances the unloading of oxygen into tissues to meet the oxygen demand of the tissue.

Question 60

Does all of the O2 that is carried around in the blood diffuse out?

Answer 60

No, much of the O2 carried does not diffuse out.