Outline

Introduction

Protein Complexity (Figure 5.1)

Amino Acids

Structure of the -amino acids (Figure 5.2, Figure 5.3)

Amino group attached to carbon (next to carboxyl carbon)
Side chains
Zwitterions

Stereochemistry of the -amino acids (Figure 5.4)

Chiral center/Stereocenter

Asymmetric carbon

Stereoisomers/Enantiomers/Optical isomers (Figure 5.5)
L-amino acids (predominant form in polypeptides)

Drawn in this book with amino to left, carboxyl to right, R group on top
Glycine is only amino acid in proteins with asymmetric carbon - so is not chiral.

D-Amino acids (rare - occur in some bacterial polypeptides)(Table 5.2)

It is possible to chemically synthesize proteins with D-amino acids.

Properties of Amino Acid Side chains: Classes of -Amino Acids (Table 5.1, Figure 5.3)

Aliphatic side chains (a diverse group - more nonpolar ones, such as VAL, LEU, ILE prefer interior of protein molecule)

Glycine, Alanine, Valine, Leucine, Isoleucine, Proline

Hydroxyl or Sulfur-Containing Side Chains (weakly polar side chains, except MET)

Serine, Cysteine, Threonine, Methionine

Aromatic Amino Acids (Strong absorption of light in near UV) (Figure 5.6)

Phenylalanine, Tyrosine, Tryptophan

Basic Amino Acids (Strongly polar, usually on exterior of proteins) (Figure 5.7)

Histidine, Lysine, Arginine

Acidic Amino Acids and Their Amides (ASP and GLU strongly acid, ASN and GLN polar but not charged. All prefer exterior of protein)

Aspartic Acid, Glutamic Acid, Asparagine, Glutamine

Modified Amino Acids

O-Phosphoserine
4-Hydroxyproline
-Hydroxylysine
-Carboxyglutamic acid

Peptides and the Peptide Bond (Figure 5.8)

Peptides (amide bond between amino and carboxyl groups) (Figure 5.9, Figure 5.10)

Dipeptide contains 2 amino acids linked by a peptide bond
Oligopeptide contains a few amino acids joined by peptide bonds
Polypeptide contains many amino acids joined by peptide bonds
All proteins are polypeptides

Polypeptides as Polyampholytes (Figure 5.11)

Small pH changes can significantly alter protein charge and properties

Structure of the Peptide Bond (Figure 5.12)

Double bond character of peptide bonds makes C,N,H,O nearly coplanar (Figure 5.12)

Stability and Formation of the Peptide Bond (Unnumbered Figure, Table 5.4)

Hydrolysis of peptide bond favored energetically, but uncatalyzed reaction very slow
Strong mineral acid, such as 6 M HCl, good catalyst for hydrolysis
Proteolytic enzymes (proteases) provide catalysis for cleaving specific peptide bonds
Cyanogen bromide cleaves peptide bonds at specific point too - on carboxyl side of methionines (Figure 5.13)
Amino acids must be "activated" by ATP-driven reaction to be incorporated into proteins (Figure 5.19)

Proteins: Polypeptides of Defined Sequence (Figure 5.14, Figure 5.15)

Amino acid composition
Amino acid sequence

From Gene to Protein

The Genetic Code (Three nucleotides - codon - code for one amino acid in a protein) (Figure 5.16, Figure 5.17, Figure 5.18)

Translation (Figure 5.19, Figure 5.20)

Translation is the process of "reading" the codons and linking appropriate amino acids together through peptide bonds
tRNAs carry amino acids for translation
Translation is accomplished by the anticodon loop of tRNA forming base pairs with the codon of mRNA in ribosomes
Stop codons act to stop translation

Posttranslational Processing of Proteins (Figure 5.21)

Folding
Amino acid modification (some proteins)
Proteolytic cleavage (some proteins - insulin is an example) -

1. Insulin is synthesized as a single polypeptide called preproinsulin with leader sequence to help it be transported through the cell membrane.

2. Specific protease cleaves leader sequence to yield proinsulin.

3. Proinsulin folds into specific 3D structure and disulfide bonds form

4. Another protease cuts molecule, yielding insulin, which has two polypeptide chains