Biochemistry Chapter 5

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BiochemistryChapter 5

• Introduction to Proteins
• The primary Level of Protein Structure
• Mak Oi Tong

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Introduction

• Protein Complexity -myoglobin, (Figure 5.1)
• Roles of proteins e.g. enzymes

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Fig. 5.1
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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

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Fig. 5.2
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Fig. 5.3a
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Fig. 5.3b
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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 the 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.

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Fig. 5.4
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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 the 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.

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Fig. 5.5
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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 the 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.

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Table 5.2
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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

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Fig. 5.6
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• 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

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Fig. 5.7
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Modified Amino Acids

• O-Phosphoserine
• 4-Hydroxyproline
• d-Hydroxylysine
• ?-Carboxyglutamic acid

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Peptides and the Peptide Bond (Figure 5.8)

• Condensation of amino acids to form peptide
  bonds.
• Similar to -CC- bond.

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Fig. 5.8
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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

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Fig. 5.9
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Fig. 5.10
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Polypeptides as Polyampholytes (Figure 5.11)

• Small pH changes can significantly alter protein
  charge and properties

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Fig. 5.11
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Structure of the Peptide Bond (Figure 5.12)

• Double bond character of peptide bonds makes C,
  N, H, O nearly coplanar

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Fig. 5.12
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Stability and Formation of the Peptide Bond
(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 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)

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Stability and Formation of the Peptide Bond
(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)

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Fig. 5.13
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Stability and Formation of the Peptide Bond
(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)

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Fig. 5.19
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Proteins

• Polypeptides of Defined Sequence
• (Figure 5.14, Figure 5.15)
• Amino acid composition
• Amino acid sequence

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Fig. 5.14
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Fig. 5.15
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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

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Fig. 5.16
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Fig. 5.17
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Fig. 5.18
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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

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Fig. 5.19
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Fig. 5.20
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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

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Fig. 5.21