Survey of Biomolecules Part III:Amino Acids, Peptides, and Proteins
Lecture Supplement:
Take one handout from the stage
Why Bother With Protein Structure?
Structure controls function
Enzyme selectivity
Drug design
Many others

Fundamental protein structure = amide polymer
Basic building block of protein structure = amino acid
All have amine and carboxylic acid groups
All are primary amines (-NH2) except proline
Side chains attached to a-carbon vary
Most have S configuration at a-carbon, except glycine (R = H)
Amine + carboxylic acid = proton transfer possible
Amino Acids
Keq > 1 at physiological pH
Neutral (unionized) form
Zwitterionic (ionized) form
Amino Acids
The 21 natural amino acids categorized by side chain properties:
Hydrophilic versus hydrophobic

Hydrophobic nonacidic side chains
Acidic versus basic versus neither (nonacidic)
Amino Acids
Hydrophobic acidic side chains
Cysteine (Cys)
Selenocysteine (Sec)
Rare
Hydrophilic nonacidic side chains
Amino Acids
Hydrophilic acidic side chains
Hydrophilic basic side chains
Amino Acids Form Peptides
Amino acids link via peptide bond (an amide); form chains
Example:
Serine rotation?
Amino Acids Form Peptides
A tripeptide (three amino acids)
Naming: Val-Ser-Ala or Ala-Ser-Val? N-terminus  C-terminus
N-terminus
C-terminus
Ala
Ser
Val
Amino acid sequence = primary structure
Like amino acids, peptides and proteins also have zwitterionic forms:
How Does Peptide Bond Influence Structure?
Trans
Amino acid chain
opposite sides C-N bond
Cis
Amino acid chain
same side of C-N bond
Torsional strain: trans < cis; equilibrium favors trans isomer by ~ 2 kcal mol-1
Conjugation effects:
Barrier to rotation around C-N bond ~16 kcal mol-1
Amide is conjugated:
The Protein Conformation Problem
Consider major conformational isomers of a glycine peptide:
Each glycine has 2 x 3 x 3 = 18 major conformations Verify with models
A small protein consisting of 14 glycine has 1814 = 3.8 x 1017 major conformations!
Number of conformations  significantly if more amino acids, or side chains present
Problem: Protein function requires well-organized and restricted structure
Solutions:
Local conformational restrictions: cis/trans isomers and planarity
Intramolecular hydrogen bonds
Results:
Reduced protein flexibility
Reduced structure randomness
Secondary Structure
Structural randomness reduced by intramolecular hydrogen bonds
Causes three basic motifs: the secondary structures of proteins
a-Helix
Clockwise spiral down
H-bonds parallel to axis
Side chains point out from center
Elastic coil: Thinkbook binding
Secondary Structure
b-Sheet: Two or more aligned, H-bonded amino acid chains
Parallel (N-termini same end) or antiparallel (N-termini opposite ends)
The illustrated b-sheet is antiparallel
b-Sheet more rigid/less elastic than a-helix
Significant component of keratin (hair, wool) and silk
Make your own silk: Thinkbook page 100
N-terminus
C-terminus
C-terminus
N-terminus
Secondary Structure
(Random) Coil: not really random, just hard to describe
Tertiary Structure
Tertiary structure: aspects of protein structure determined by side chain composition
Response to environment: side chain orientation depends on environment
Disulfide bridges: form loop within one chain, or bond two separate chains
Found in:
Insulin (3)
Keratin (hair)
Others
Quaternary Structure
Quaternary structure: association of two or more subunits by noncovalent bonds
Subunits = polypeptides, carbohydrates, coenzymes, etc.
Large surface areas  noncovalent forces can be significant magnitude
Protein Structure Representations
Myoglobin
stores O2 in muscle tissue via heme
~70% a-helix
a globular protein (~spherical shape)
Protein Structure Representations
Retinol Binding Protein
Important for vision
Protein Structure Representations
Lactate Dehydrogenase
Released in bloodstream by damaged muscles
Indicative of heart damage or failure
Quaternary structure = four identical units
Subject of Chem 153L experiments