AA peptides, and proteins

Question 1

non-polar aliphatic AA

Answer 1

Glycine, alanine, valine, leucine, methionine, isoleucine

Question 2

polar uncharged AA

Answer 2

syrine, threonine, cysteine, proline, asparagine, glutamine

Question 3

positively charged AA

Answer 3

lysine, arginine, histidine

Question 4

negatively charged AA

Answer 4

aspartate, glutamate

Question 5

non-polar aromatic AA

Answer 5

phenylalanine, tyrosine, tryptophan

Question 6

Describe the function of disulphide bonds within proteins

Answer 6

Important for tertiary structure of proteins, adding stability and changes in shape to proteins.

Question 7

Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; hydroxylation

Answer 7

Hyrdroxylation: Hydropxyproline: hydroxyl group added. Important in collagen structure where L handed helixes are stabilized by H bonds with this. Scurvy: enzyme hydroxylating proline needs vitamin c to act

Question 8

Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; Carboxylation

Answer 8

Carboxylation: Carboxyglutamate: addition of carboxyl group to glutamate. Necessary in certain clotting factors. Warfarin inhibits enzyme function. Vitamin k deficiency: enzyme needs K to add carboxyl group to glutamate, results in insufficient clotting

Question 9

Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; glycosylation

Answer 9

O linked: Ser and Thr N linked: Asparagine If mutated: congenital disorder of glycosylation, leads to severe or fatal disorder involving nervous system, muscle, instestines

Question 10

Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; Acetylation or Methyaltion

Answer 10

Lys: can be acetylated or methylated Drugs: Vorinostat or HDAC Arg: can be methylated Important in chromatin remodeling, HATS will acetylate, negate positive charge

Question 11

Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; Acetylation or Methyaltion

Answer 11

Lys: can be acetylated or methylated Drugs: Vorinostat or HDAC Arg: can be methylated Important in chromatin remodeling, HATS will acetylate, negate positive charge

Question 12

Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; Reversible phosphorylation

Answer 12

Ser, Thr, Tyr can be reversibly phosphorylated CML (leukemia) patients have fusion protein which causes kinase to be constantly active, constant proliferation Drug, geelvec, competitively bind and inhibits overactive protein

Question 13

Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; ubiquitination

Answer 13

• Normally ubq marks cells for proteasome destruction - Drug: bortezomib (Velcade) acts to prevent ubiquitination, thus inhibiting cells ability to degrade protein, accumulation of protein occurs and results in cell death

Question 14

Distinguish three covalent bonds including the peptide bonds that make the backbone of a polypeptide chain.

Answer 14

φ (phi): angle around the C—amide nitrogen bond ψ (psi): angle around the C—carbonyl carbon bond Peptide bond itself cannot rotate due to partial double bond

Question 15

Distinguish that the amino acid sequence determines the function; mutations in amino acid sequence can cause genetic disease (give example)

Answer 15

Sickle cell anemia; caused by single AA change (glutamate to valine)

Question 16

Recognize that proteases and the specific breaking of peptide bonds can have important functions.

Answer 16

Proteases can either digest any protein (digestion) or specific proteins at specific peptide bonds. Certain proteins need to be cleaved in order to fold correctly and become functional Ex) Thrombin and clotting cascade

Question 17

Describe hydrogen bonds and their role in secondary structure formation.

Answer 17

H bonds form between multiple R groups, the NH backbone, and the O backbone In alpha helix, have H bonding between backbone NH and O, occurring every 4 AA In beta sheets, have H bonding between H bonds in neighboring sheets.

Question 18

Describe secondary structure alpha helix

Answer 18

R handed helix that is very tight (nothing can fit within it) H bonds within backbone every 4 AA Bind well within major groove DNA Residues 1 and 8 fit nicely overtop each other

Question 19

Describe secondary structure Beta sheet

Answer 19

Pleated sheet like structure H bonds between backbone of neighboring strand Side chains protrude alternating up and down Can be parallel or antiparallel (antiparallel more stable)

Question 20

Explain tertiary structures

Answer 20

Overall spatial arrangement of atoms in protein. Two major types: Fibrous proteins: Single secondary structure, insoluble Globular proteins: Multiple secondary structures, water and lipid soluble

Question 21

Explain quaternary structures

Answer 21

Multiple separate tertiary structures coming together to form single protein (hemoglobin)

Question 22

Explain the role of loops in protein structure and function.

Answer 22

Certain amino acids unable to form secondary structure, loops instead form (gly and pro) Leads to differential folding Differential function, ie immunoglobulin variable domains, collagen

Question 23

Explain how to use Kd to represent binding strength.

Answer 23

Kd represents the amount of ligand needed to bind half of a certain protein. Lower the Kd, the higher affinity the ligand has for a protein

Question 24

Explain how binding specificity can be achieved

Answer 24

Lock and Key Protein binding site and ligand are complementary in size, shape, charge, hydrophobic/philic character. fit together like lock and key. Induced fit Upon first ligand binding, a conformational change occurs in protein that increases its affinity for another ligand

Question 25

Explain how heme enables myoglobin to bind oxygen.

Answer 25

Proteins cannot bind O2 Need metal to be able to bind O2, Fe binds to O2 without the generation of free radicals, advantage over transition metals. Histidine residues (heme) protect Fe and prevent it from being oxidized

Question 26

Explain the molecular basis of carbon monoxide poisoning.

Answer 26

Similar in size to O2, CO binds 20,000 times more strongly than O2, protein pocket decreases the strength of this bond to 250 times (still irreversible)

Question 27

Explain why hemoglobin is a good oxygen transporter.

Answer 27

Hemoglobin has positive cooperativity. For every oxygen it binds, increases affinity for additional molecules. In lungs with high pO2, every site is bound to oxygen, will induce change to relaxed conformation. As it moves throughout the body and pO2 drops, it begins to lose oxygen and dramatically drops affinity for oxygen, converts to tense state. Drops affinity low enough in tissues to have higher binding affinity for CO2