Lecture 8: Protein Structure and Function

Question 1

_____\_: Lysine residues of protein targets proteins for degradation in the proteasome

Answer 1

Ubiquitinoylation: Lysine residues of protein targets proteins for degradation in the proteasome

Question 2

Histone Ubiquitinylation:

• H2A and H2B ubiquitinylated
• Not related to degradation
• Affects _____\_structure and __________\_

Answer 2

Histone Ubiquitinylation:

• H2A and H2B ubiquitinylated
• Not related to degradation
• Affects chromatin structure and gene transcription

Question 3

Histone Ubiquitinylation effects:

– ______\_ alignment and segregation

– _______\_ repair

– Transcriptional response in ______\_

Answer 3

Histone Ubiquitinylation effects:

– Chromosome alignment and segregation

– DNA repair

– Transcriptional response in inflammation

Question 4

__________: Addition of phosphate via protein Kinase

Answer 4

Phosphorylation: Addition of phosphate by protein kinase

Question 5

_____________\_: Kinase activity affected by another kinase, which in turn affects multiple molecules of another

Answer 5

Kinase cascade: Kinase activity affected by another kinase, which in turn affects multiple molecules of another

Question 6

Phosphorylation:

_______ charges change the structure

Can affect the binding site of ligands elsewhere on protein

Access of Substrate to the active site

Answer 6

Phosphorylation:

Negative charges change structure

Can affect binding site of Ligands elsewhere on protein

Access of Substrate to active site

Question 7

What is the T-Loop?

Answer 7

Gate that covers the active binding site till it becomes negatively charged via phosphorylation

Question 8

Kinase families have similar functions/roles:

• __________ across plasma membrane
• Intracellular signal amplification
• Cell cycle control

Answer 8

Kinase families have similar functions/roles:

• Signal transduction across plasma membrane
• Intracellular signal amplification
• Cell cycle control

Question 9

The Bcr-Abl __________\_ oncogene causes chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL

This enzyme remains stuck in activated form and induces excessive proliferation of ____\_

Treatment?

Answer 9

The Bcr-Abl tyrosine kinase oncogene causes chronic myelogenous leukemia (CML) and Philadelphia chromosome- positive acute lymphoblastic leukemia (ALL)

The enzyme remains in activated form. Induces excessive proliferation of WBCs

Imatinib (GLEEVEC) binds to the site of tyrosine activity and prevents its activity. Served as model for other targeted therapy modalities

Question 10

Role of proteins: (7)

Answer 10

• Enzymes
• Transport
• Contraction
• Protection
• Hormones
• Control of transcription/translation
• Structure

Question 11

___________:

Binds Oxygen in Muscles

7 Helices

1 Heme w/ iron

Answer 11

Myoglobin:

Binds Oxygen in Muscles

7 Helices

1 Heme w/ iron

Question 12

__________:

Transports Oxygen in the blood

Tetramer: Can bind with 4 molecules of oxygen, one to each ­­________\_

2 alpha chains and 2 beta chains

Cooperative Interaction?

Answer 12

Hemoglobin:

Transports Oxygen in blood

Tetramer: Can bind with 4 molecules of oxygen, one to each ­­Porphyrin

2 alpha chains and 2 beta chains

Cooperative Interaction: Once first binds, second binds more easily_,_ and so on

Question 13

Each subunit of hemoglobin is a _________ protein with an embedded ______ group

Answer 13

Each subunit of hemoglobin is a globular protein with an embedded heme group

Question 14

In sickle cell hemoglobin ___________\_ in position 6 (in beta chain) is mutated

to ____\_. This change causes the ________\_ form of hemoglobin molecules to stick together

Answer 14

In sickle cell hemoglobin glutamic acid in position 6 (in beta chain) is mutated

to valine. This change causes the deoxygenated form of hemoglobin molecules to stick together

• Hemoglobin relies on negative charge of Glutamic acid to repel from one to another*
• When changed to Valine w/ no charge the molecules stick together*

Question 15

______\_: Group of genetic disorders characterized by errors in metabolic pathways of heme synthesis.

Answer 15

Phorias: Group of genetic disorders characterized by errors in metabolic pathways of heme synthesis.

Question 16

____________:

Also known as antibodies, are glycoprotein molecules produced by white blood cells. They act as a critical part of the immune response by specifically recognizing and binding to particular antigens, such as bacteria or viruses

Answer 16

Immunoglobulins:

Also known as antibodies, are glycoprotein molecules produced by white blood cells. They act as a critical part of the immune response by specifically recognizing and binding to particular antigens, such as bacteria or viruses

Question 17

_________: Protein that aids in coagulation and protects against blood loss

Answer 17

Fibrin: Protein that aids in coagulation and protects against blood loss

Question 18

Antibody Structure:

Shuffling of peptides allows for very specific binding of specific antigens

All of the diversity of antibody binding is attributed to changing less than a dozen proteins in the ___________\_

Answer 18

Antibody Structure:

Shuffling of peptides allows for very specific binding of specific antigens

All of the diversity of antibody binding is attributed to changing less than a dozen proteins in the hyper-variable region

Question 19

Complementarity Determining Region (CDR_)_ = ________\_

Answer 19

Complementarity Determining Region (CDR_)_ = Antigen binding site

Question 20

Enzymes:

• Reduce ______\_ energy of reaction
• Remain unchanged so can be re- used again and again
• Effective in ____\_ amounts
• Enzymes can cause reactions to occur up to 10 billion times easier than when no enzyme is present

Answer 20

Enzymes:

• Reduce activation energy of reaction
• Remain unchanged so can be re- used again and again
• Effective in small amounts
• Enzymes can cause reactions to occur up to 10 billion times easier than when no enzyme is present

Question 21

________: molecule on which an enzyme acts

Answer 21

Substrate: molecule on which an enzyme acts

Question 22

Standard chemical reaction: rate of reaction is _______\_ to the concentration of substrate

Answer 22

Standard chemical reaction: rate of reaction is directly proportional to the concentration of substrate

Question 23

Enzyme-catalyzed reaction: rate of reaction ______\_ increase further with increasing concentration of substrate

Answer 23

Enzyme-catalysed reaction: rate of reaction doesn‘t increase further with increasing concentration of substrate

Saturated when the active site of all of the enzyme molecules present are occupied

Question 24

__________: Inhibition or activation of an enzyme by a small regulatory molecule that interacts with the enzyme at a site other than the active site. Interacts ______\_ with enzyme

Answer 24

Allosteric Regulation: Inhibition or activation of an enzyme by a small regulatory molecule that interacts with the enzyme at a site other than the active site. Interacts non-covalently with enzyme

Question 25

___________\_ - enzyme permanently inactivated. Example?

Answer 25

Irreversible inhibition - enzyme permanently inactivated.

e.g.Aspirin irreversibly inactivates the cyclooxygenase (COX) enzyme required for prostaglandin and thromboxane synthesis

Question 26

_______ inhibition - the enzyme can function normally when the inhibitor is diluted or removed

Answer 26

Reversible inhibition - the enzyme can function normally when the inhibitor is diluted or removed

Question 27

___________ Inhibition: Interferes with active site of enzyme so substrate cannot bind

Answer 27

Competitive Inhibition: Interferes with active site of enzyme so substrate cannot bind

Question 28

__________ Inhibition: Changes shape of enzyme so it cannot bind to substrate

Answer 28

Non-Competitive Inhibition: Changes shape of enzyme so it cannot bind to substrate

Question 29

_________\_ can be detected by measuring enzymes that leak into the blood

Answer 29

Tissue damage can be detected by measuring enzymes that leak into the blood