Amino Acids

Question 1

Increasing Hydrophobicity

Answer 1

Larger chains of CH3= greater hydrophobicity (more carbon hydrogen chains will repel water better)

Aromatic Groups= less or no hydroxyl groups means more hydrophobic

Question 2

Disulfide Bridge

Answer 2

Cysteine form Sulfur-Sulfur bonds.

Ex: Inside insulin
Cys—-S–S——Cys

Question 3

Positively Charged R groups

Answer 3

Histidine, Lysine, and Arginine.

Lysine and Arginine will bring their positive
Basic?

Question 4

Polar and Negatively Charged

Answer 4

Aspartate and Glutamate

Question 5

Essential Amino Acids

Answer 5

Arganine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylaline, Threonine, Tryptophan, Valine
10 essential amino acids.

Question 6

Scurvy

Answer 6

Rich in collagen.

Lacking in Hydroxyrproline.

Question 7

Y- carboxyglutumate

Answer 7

Present in several blood clotting factors.

Vitamin K deficiency= Warfarin

Question 8

Glycosylation

Answer 8

O linked glycosylation: Sugars added to Ser or Thr

N linked glycosylation: Sugars added to the asparagine in the
sequences -X-N-X-S/T-

Question 9

Gleevec

Answer 9

a bcr-abl tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML)

Question 10

Peptide bond and peptide plane

Answer 10

Rotation around the peptide bond not permitted

Rotation around ψ and φ (dihedral angles) permitted
φ (phi): angle around the C—amide nitrogen bond
ψ (psi): angle around the C—carbonyl carbon bond
In a fully extended polypeptide, ψ and φ are 180°

Question 11

Secondary structures: a local spatial arrangement of the polypeptide chain

Answer 11

Alpha Helices: 30%
Beta Pleated Sheets: 30%

Turns and Loops
Triple Helix (as seen in collagen)

Question 12

α-helix

Answer 12

H-bonds between backbone carbonyl (CO) and amine (NH) within a polypeptide chain forms the α-helix

A right -handed screw
H-bonds between CO of residue n and the NH of residue n+4
Ex: Leucine zipper

Small hydrophobic residues such as Ala and Leu are strong helix formers

Pro and Gly are helix breakers

Structural fibrous proteins Keratin-hair, nails, horns
Myosin
Tropomyosin
fibrinogen

Globular: Hemoglobin, Myoglobin

Question 13

Beta Sheets

Answer 13

The backbone is more extended
Has a pleated sheet-like structure
Hydrogen bonds between the backbone of neighboring strands
Side chains protrude from the sheet alternating in up and down direction

Question 14

Secondary Structure: β Turns

Answer 14

β-turns occur frequently whenever strands in β sheets change the direction
The 180° turn is accomplished over four amino acids
The turn is stabilized by a hydrogen bond from the carbonyl oxygen of the 1st amino acid to amide proton of the 4th amino acid
Proline in position 2 or glycine in position 3 are common in β-turns

four amino acids turn

• hydrogen bond between the 1st and the 4th amino acid
• Proline in position 2 or glycine in position 3 are common

Question 15

Proline Isomers

Answer 15

Most peptide bonds are in the trans configuration
For peptide bonds involving proline, ~6% are in the cis configuration.
Proline isomerization is catalyzed by prolyl isomerases

Question 16

Protein Tertiary Structure

Answer 16

-overall spatial arrangement of atoms in a polypeptide chain or in a protein
-Two major classes
fibrous proteins
¤ typically insoluble; made from a single secondary structure
globular proteins
water-soluble globular proteins
lipid-soluble membraneous proteins

Question 17

Motifs (folds)

Domains

Answer 17

Arrangements of several secondary structure elements

Many proteins are made up of multiple stable globular units called domains. Domains have more-or-less independent functions.

Question 18

Quaternary Structure

Answer 18

Quaternary structure is formed by multiple polypeptides into a larger functional cluster

Question 19

Structure of Collagen

Answer 19

Collagen is an important constituent of connective tissue: tendons, cartilage, bones, cornea of the eye
Each collagen chain is a long Gly- and Pro-rich left-handed helix
Three collagen chains intertwine into a right-handed superhelical triple helix
The triple helix has higher tensile strength than a steel wire of equal cross section

Question 20

Structure and functions of Globular Proteins

Answer 20

Storage of ions and molecules 
-myoglobin, ferritin 
Transport of ions and molecules 
-hemoglobin, serotonin transporter
Defense against pathogens 
-antibodies, cytokines 
Muscle contraction 
-actin, myosin 
Biological catalysis 
-chymotrypsin, lysozyme

Question 21

Function of Myoglobin

Answer 21

Need to store oxygen for metabolism
Protein side-chains lack affinity for O2
Some transition metals bind O2 well but would generate free radicals if free in solution
Organometallic compounds such as heme are more suitable but Fe2+ in free heme could be irreversibly oxidized to Fe3+ which no longer binds oxygen
Solution:
Bury heme and bound oxygen inside the protein
In mammals, myoglobin is the main oxygen storage protein

Question 22

Hemoglobin and cooperativity

Answer 22

Must be a protein with multiple binding sites
Binding sites must be able to interact with each other
This phenomenon is called allostery or cooperativity
positive cooperativity: first binding event increases affinity at remaining sites
negative cooperativity: first binding event reduces affinity at remaining sites

Hemoglobin is a tetramer of two subunits (α2β2)
Each subunit is similar to myoglobin
The four subunits interact with each other

Blood in lungs has higher pH than blood in metabolic tissues
Affinity for oxygen depends on the pH
Oxygen binds well at higher pH
Oxygen is released well at lower pH
The pH difference between lungs and metabolic tissues increases the O2 transfer efficiency
This is known as the Bohr effect

Question 23

Hemoglobin also Transports H+ and CO2

Answer 23

CO2 is produced by metabolism in tissues and must be exported
Some CO2 exported as dissolved bicarbonate in the blood
Some CO2 is exported in the form of a carbamate on the amino terminal residues of each of the hemoglobin subunits.

Question 24

Protein Structure Methods:

X-Ray Crystallography

Answer 24

Steps needed:
Purify the protein
Crystallize the protein
Collect diffraction data
Calculate electron density
Fit residues into density

Pros:
No size limits

Cons:
Crystallization is the rate-limiting step

Question 25

Structure Methods:

Biomolecular NMR

Answer 25

Steps needed:
Purify the protein
Dissolve the protein
Collect NMR data
Assign NMR signals
Calculate the structure

Pros:
No need to crystallize the protein

Cons:
Need very concentrated proteins
Very difficult for large proteins (

Question 26

The first class of chaperones: Hsp70/Hsp40

Answer 26

prokaryotic homologs: DnaK and DnaJ
induced at elevated temperatures
bind to hydrophobic region of unfolded protein and prevent aggregation
help transport some proteins cross membranes in unfolded states

Question 27

Some protein folding pathways require protein disulfide isomerase (PDI)

Answer 27

Secreted or cell surface proteins.

The correct disulfide bonds often do not form on their own in proteins with many free cysteines.

Protein disulfide isomerase reduces improper disulfide bonds and reform them correctly.