Amino Acids, peptides, proteins I

Question 1

What is an AA?

Answer 1

Amino acids are building blocks of peptides and proteins. Each amino acid is made of a C-alpha atom, an amino group, a carboxyl group, and a side chain R group. Amino acid is a dipolar ion at physiological pH, with its amino group carrying a positive charge, while its carboxyl group carries a negative charge.
The side chain group gives each amino acid unique properties.

Question 2

Side chains?

Answer 2

non-polar/aliphatic amino acids (G, A, V, L, M, I); glycine, alanine, valine, leucine, methionine, isoleucine
aromatic amino acids (Y, W, F): tyrosine, tryptophan, phenylalanine
Polar and uncharged amino acids (T, S, C, P, N, Q); threonine, serine, cysteine, proline, asparagine, glutamine
polar and charged amino acids (H, K, R); histidine, arginine, lysine
and polar and negatively charged amino acids (D, E).: glutamic acid, aspartic acid

Question 3

Cysteine can

Answer 3

Form disulfide bonds

Question 4

why are disulfide bonds important?

Answer 4

Stabilization and conformation of proteins
Often formed by cysteine (polar and uncharged) residues
Structure is important for proper fx.
Also help with proper folding

Question 5

Major post-translational covalent modifications of AA side chains in proteins?

Answer 5

1. ) Add OH group to proline
2. ) Carboxylation of gluatamate
3. ) Glycosylsation O-linked: added to serine or threonine. N-linked: sugar added to asparagine
4. ) Acetylation and methylation
5. ) Reversible phos/dephos
6. ) Ubiquination

Question 6

OH group to proline

Answer 6

1.) Add OH group to proline to make hydroxylproline. Need Vitamin C for this. If you have SCURVY you also have collagen problems b/c collagen rich in hydroxyproline.

Question 7

Carboxylation of glutamate

Answer 7

2.) Carboxylation of gluatamate: carboxyglutamate is important in proteins that help with blood clotting. Vit K is needed for the enzyme that carboxylates glutamate (so Vit K deficiency = trouble clotting)
Anti-clotting medicine is warfarin, antagonizes Vit K recycling

Question 8

Glycosylation O or N-linked

Answer 8

3.) Glycosylsation O-linked: added to serine or threonine. N-linked: sugar added to asparagine (addition of the sugar mlc can help proteins become more soluble). Can also play a role in adhesion b/w cells. Cell-cell clygocproteins. If glycosylation doesn’t happen you get congenital disorder of glcosylation (CDG).

Question 9

Acetylation and methylation

Answer 9

Of lysine and arginine. Happens commonly on histone proteins. NOrmally they are positively charged and helps them bind to DNA. Acetylation or methylation neutralizes the charge and changes the DNA/histone interactions… leads to serious issues with DNA repair etc.
Vorinostat and HDAC inhibs. Remove acetyl and get condensed/trx silenced chromatin.

Question 10

Reversible phos/dephos

Answer 10

Of hydroxyl groups of serine, threonine, and tyrosine

Gleevec: bcr-abl tyrosine kinase inhib. Bcr-able is stuck in on position in CML and keeps adding P to things, so drug stops this and cells die

Question 11

Ubiquination

Answer 11

Largest modification. Add a 76 AA protein to other proteins onto LYSINE residues
Polyubiq proteins are destined for degradation by proteosomes.
Bortezomib/Velcade: first therapeutic proteosome inhibitor tested in humans for multiple myeloma. Prevents degradation of ubiq proteins.