Exam 1: Amino Acids & Proteins

Usually four amino acids; often contain proline and glycine

What are key features of a β-turn?

Side-chain properties

What primarily determines whether an amino acid tends to be located in the interior or exterior of a folded protein?

Glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline

Which amino acids are classified as nonpolar/hydrophobic in this lecture?

Serine, threonine, tyrosine, asparagine, glutamine, cysteine

Which amino acids are classified as uncharged polar in this lecture?

Aspartate and glutamate

Which amino acids have acidic side chains?

Histidine, lysine, and arginine

Which amino acids have basic side chains?

L-amino acids

Which stereochemical form of amino acids is found in proteins?

The R group / side chain

What determines the distinctive chemical properties of an amino acid?

Rigid and planar

What is the structural character of a peptide bond?

Rotation around bonds involving the Cα

Where can the peptide backbone rotate if the peptide bond itself is planar?

A molecule carrying both positive and negative charges

What is a zwitterion?

Nonpolar / hydrophobic side chains

Which type of amino-acid side chain is usually found in the interior of a folded globular protein?

Hydrophilic / polar side chains

Which type of amino-acid side chain is usually found on the exterior of a globular protein in contact with water?

Aspartate and glutamate

Which amino acids have acidic side chains?

Negatively charged

What charge do aspartate and glutamate side chains typically carry at physiologic pH?

Histidine, lysine, and arginine

Which amino acids have basic side chains?

Positively charged

What charge do lysine and arginine side chains typically carry at neutral pH?

About 6.0

What side-chain pKa is emphasized for histidine?

About 8.3

What side-chain pKa is emphasized for cysteine?

Below pKa = mostly protonated; above pKa = mostly deprotonated

How does pH relative to pKa determine protonation state of an amino-acid side chain?

Cysteine

Which amino acid contains a sulfhydryl group that can form disulfide bonds?

Cystine

What is the dimer formed when two cysteine side chains form a disulfide bond?

The pH at which positive and negative charges are equal and net charge is zero

What is the isoelectric point (pI)?

pI = (pK1 + pK2)/2

What equation is given for the isoelectric point of the simple amino acid case?

Amino-acid sequence

What is primary protein structure?

N-terminus → C-terminus

In what direction are protein sequences written?

Alpha helices and beta sheets

What are the major examples of secondary protein structure?

Hydrogen bonds between backbone peptide-bond groups

What mainly stabilizes secondary protein structure?

Proline

Which amino acid commonly breaks an alpha helix or creates a turn?

Four residues away

In an alpha helix, each carbonyl group hydrogen bonds to an N-H group how many residues away?

Parallel or antiparallel

What are the two orientations of beta sheets?

The 3-D spatial relationship of all amino acids in one polypeptide

What is tertiary protein structure?

Disulfide bonds, hydrophobic interactions, hydrogen bonds, and ionic bonds

What major interactions stabilize tertiary protein structure?

Arrangement of separate polypeptide subunits into a functional protein

What is quaternary structure?

Primary → secondary → domain → subunit → protein

What folding order is emphasized in the professor review?

Primary structure

Where is most of the information needed for a protein to fold encoded?

Release of ordered water around hydrophobic side chains

What entropy-related effect helps drive protein folding?

The hydrophobic effect

What is the name of the folding-driving effect produced when burial of hydrophobic groups frees ordered water?

Reduce barriers between folded states and decrease the chance of folding dead ends

What do molecular chaperones do?

A glutamate-to-valine substitution in β-globin

What amino-acid substitution causes HbS in sickle cell disease?

Low oxygen tension

What condition promotes HbS aggregation?

A hydrophobic protrusion that fits into a hydrophobic site on another HbS molecule

How does the HbS valine substitution promote aggregation?

Amyloid-β plaques and abnormal tau neurofibrillary tangles

What protein-misfolding features are associated with Alzheimer disease in this lecture?

Alpha-synuclein forming Lewy bodies

What protein-misfolding feature is associated with Parkinson disease?

Normal prion protein that is monomeric and rapidly turned over

What is PrPc?

Misfolded prion form that assembles into long-lived fibrils/polymers

What is PrPsc?

False — normal PrPc does not normally form brain fibers

Is the normal function of PrPc to form fibers in the brain?