2 - Basic Amino Acid Structure and Chemistry Flashcards
What are the building blocks of a cell?
Proteins, carbohydrates, lipids, and nucleic acids
What do amino acids do?
Determine shape/function of proteins, specific chemical reactions (catalysis)
What do carbohydrates do?
Storage, generation of energy, structure, signaling
What do lipids do?
Components of cell membranes, signaling molecules
What do nucleic acids do?
Building blocks of DNA/RNA, source of energy in coupled reactions (ATP), signaling, activation of substrates
What is the general structure of an amino acid?
H3N+ - CHR - COO-
What implicit conditions are present for amino acids?
Neutral (pH = 7.4)
What is the charge on a general amino acid at pH = 7.4?
Positive amine (protonated), negative carboxylic acid (deprotonated)
What configuration do all natural amino acids have?
L configuration
What is the L configuration of an amino acid?
- Look down H-C bond
2. CO - R - N is clockwise
What stereochemistry do most amino acids have?
S configuration
Which amino acid has R configuration?
Cysteine
How come cysteine has R configuration?
S (side chain) has higher priority than N
What is S configuration?
Counterclockwise decrease in priority based on atomic number
What is R configuration?
Clockwise decrease in priority based on atomic number
True or false: all natural amino acids are L
True: all amino acids are L
True or false: all natural amino acids are S
False: cysteine is R, and glycine is achrial
True or false: all amino acids are chiral
False: glycine is achiral
How are side chains usually classified?
By polarity
What do amino acid side chains do?
Control structure and properties of proteins, involved in nonpolar and electrostatic interactions, involved in enzyme catalysis
What controls protein “collapse”?
Hydrophobic interactions away from water (energetics)
What is a big factor in ligand binding?
Desolvation energy
What roles can side chains play in enzyme catalysis?
Nucleophilic catalysis, acid/base catalysis, transition state stabilization (electrostatics)
What group is found on Trp?
Indole
What group is found on Arg?
Guanidinium
What group is found on His?
Imidazolium
Which amino acid is most flexible and why?
Glycine, because it does not have a large R group
Which amino acid is least flexible and why?
Proline, because it has a ring
What reactions can aromatic side chains do?
They can accept charge well (absorbance)
What can water do with side chains?
It can satisfy charges (found near the surface)
Which amino acid(s) have two stereocenters?
Ile and Thr
What is the reactivity of His?
Versatile - acid/base, metal coordination
What is the reactivity of Cys?
Redox active, good nucleophile
What is the reactivity of Lys?
Acid, base, or nucleophile
What is the reactivity of Ser?
Can be a nucleophile when activated, phosphorylation
Which N is usually more basic: sp3 or sp2?
sp3 (less S character, LP further away)
Which N is protonated in His (sp2 or sp3)?
The sp2
Why is the sp2 N protonated in His?
It does not kill the aromaticity when protonated
What is the reactive N used for in His?
Acid/base chemistry or metal coordination
What is a tautomer?
An isomer where atoms switch places (not a resonance structure)
What is the purpose of His in carbonic anhydrase?
It forms a coordination complex around zinc, which is used to make water more electropositive to attack CO2
What type of reaction forms disulfide bonds?
Oxidation
What type of reaction breaks disulfide bonds?
Reduction
What is the significance of disulfide bonds?
They are covalent bonds, so they are less dynamic than electrostatics and H-bonds
Where are disulfide bonds used?
To facilitate folding and association
Why is SH a good nucleophile?
- SH is less electronegative
2. SH is “softer” (more polarizable)
How do cysteine proteases work?
S- acts as a nucleophile to attack and break amide bonds
If Lys is to be used as a nucleophile, what state is it in?
Deprotonated (active nucleophilic form)
If Lys is to be used for electrostatic interactions, what state is it in?
Protonated (positive charge)
What is the structure of a Schiff base?
R1R2-C=N-R3
How can Schiff bases be formed in biochemistry?
Lys can attack carbonyls (H2N)
What does phosphonoacetaldehyde hydrolase do?
It cleaves C-P bonds
How does phosphonoacetaldehyde hydrolase work?
Lys forms the Schiff base, which activates the phosphate bond, allowing water to attack and break the bond
How is lysine used in histone methyltransferase?
It can help form a good leaving group to break methyl-sulfur bond
What are some examples of spontaneous reactions with amino acids?
- Oxidation of Met
- Beta-elimination cleavage of Asp and Pro peptide bonds
- Asn deamination
What is the problem with Met oxidation?
It can lead to annoying heterogenicity in mass spectrometry
What is the problem with Asn deamination?
It can break down into Asp (change amide into hydroxyl), change the backbone (alpha to beta), and can add a double bond in the system
Where is Asn deamination a big problem?
In the pharmaceutical industry (low pH)
