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