Survey of Biomolecules Part III: Amino Acids, Peptides, and Proteins

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Survey of Biomolecules Part IIIAmino Acids,
Peptides, and Proteins

• Lecture Supplement
• Take one handout from the stage

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Why Bother With Protein Structure?

• Structure controls function
• Enzyme selectivity
• Drug design
• Many others
• Fundamental protein structure amide polymer

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Amino Acids

• 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

Keq gt 1 at physiological pH
Neutral (unionized) form
Zwitterionic (ionized) form
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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)

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Amino Acids
Hydrophobic acidic side chains
Cysteine (Cys)
Selenocysteine (Sec) Rare
Hydrophilic nonacidic side chains
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Amino Acids
Hydrophilic acidic side chains
Hydrophilic basic side chains
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Amino Acids Form Peptides
Amino acids link via peptide bond (an amide)
form chains Example
Serine rotation?
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Amino Acids Form Peptides
Ala
Ser
Val
N-terminus
C-terminus

• A tripeptide (three amino acids)
• Naming Val-Ser-Ala or Ala-Ser-Val? N-terminus
  ? C-terminus

• Amino acid sequence primary structure
• Like amino acids, peptides and proteins also have
  zwitterionic forms

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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 lt cis equilibrium
  favors trans isomer by 2 kcal mol-1

• Amide is conjugated

Conjugation effects Barrier to rotation around
C-N bond 16 kcal mol-1
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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

• Reduced protein flexibility
• Reduced structure randomness

Results
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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

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Secondary Structure
b-Sheet Two or more aligned, H-bonded amino acid
chains
C-terminus
N-terminus
C-terminus
N-terminus

• 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

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Secondary Structure
(Random) Coil not really random, just hard to
describe
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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

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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

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Protein Structure Representations

• stores O2 in muscle tissue via heme
• 70 a-helix
• a globular protein (spherical shape)

Myoglobin
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Protein Structure Representations
Retinol Binding Protein

• Important for vision

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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