Anda di halaman 1dari 47

Amino Acids and the Primary Stucture of Proteins

Important biological functions of proteins 1. Enzymes, the biochemical catalysts 2. Storage and transport of biochemical molecules

3. Physical cell support and shape (tubulin, actin, collagen)


4. Mechanical movement (flagella, mitosis, muscles) (continued)
Prentice Hall c2002 Chapter 3 1

Globular proteins
Usually water soluble, compact, roughly spherical
Hydrophobic interior, hydrophilic surface

Globular proteins include enzymes,carrier and regulatory proteins

Prentice Hall c2002

Chapter 3

Fibrous proteins

Provide mechanical support


Often assembled into large cables or threads a-Keratins: major components of hair and nails Collagen: major component of tendons, skin, bones and teeth

Prentice Hall c2002

Chapter 3

General Structure of Amino Acids


Twenty common a-amino acids

A hydrogen atom and a side chain (R)

Prentice Hall c2002

Chapter 3

Zwitterionic form of amino acids

amino acids zwitterions (dipolar ions):


Amino group = Carboxyl group = -NH3+ -COO-

Prentice Hall c2002

Chapter 3

Stereochemistry of amino acids


Gly does not have a chiral -carbon

Threonine and isoleucine have 2 chiral carbons each


Mirror image pairs of amino acids are designated L (levo) and D (dextro) Proteins are assembled from L-amino acids

Prentice Hall c2002

Chapter 3

Optical Activity
L D

Prentice Hall c2002

Chapter 3

Four aliphatic amino acid structures

Prentice Hall c2002

Chapter 3

Proline has a nitrogen in the aliphatic ring system

Proline (Pro, P) - has a three carbon side chain

heterocyclic pyrrolidine ring

Prentice Hall c2002

Chapter 3

Prentice Hall c2002

Chapter 3

10

Prentice Hall c2002

Chapter 3

11

Prentice Hall c2002

Chapter 3

12

Prentice Hall c2002

Chapter 3

13

Aromatic amino acid structures

Prentice Hall c2002

Chapter 3

14

Methionine and cysteine

Prentice Hall c2002

Chapter 3

15

Formation of cystine

Prentice Hall c2002

Chapter 3

16

Side Chains with Alcohol Groups


Serine (Ser, S) and Threonine (Thr, T) have uncharged polar side chains

Prentice Hall c2002

Chapter 3

17

Structures of histidine, lysine and arginine

Prentice Hall c2002

Chapter 3

18

Structures of aspartate, glutamate, asparagine and glutamine

Prentice Hall c2002

Chapter 3

19

Basic Lys Arg His Polar Charged Lys Arg Glu Asp His Non-polar Gly Ala
Prentice Hall c2002

Acidic Glu Asp Cys Tyr

Uncharged Asn Gln Ser Thr cys Tyr

Leu Ile
Chapter 3

Phe Try Pro


20

Val

Met

The Hydrophobicity of Amino Acid Side Chains


Hydropathy: the relative hydrophobicity of each amino acid The larger the hydropathy, the greater the tendency of an amino acid to prefer a hydrophobic environment Hydropathy affects protein folding

Prentice Hall c2002

Chapter 3

21

Hydropathy scale for amino acid residues

Prentice Hall c2002

Chapter 3

22

Compounds derived from common amino acids

Prentice Hall c2002

Chapter 3

23

Titration curve for alanine


Titration curves are used to determine pKa values pK1 = 2.4 pK2 = 9.9 pIAla = isoelectric point

Prentice Hall c2002

Chapter 3

24

Ionization of Histidine

(a) Titration curve of histidine pK1 = 1.8 pK2 = 6.0 pK3 = 9.3

Prentice Hall c2002

Chapter 3

25

Deprotonation of imidazolium ring

Prentice Hall c2002

Chapter 3

26

pKa values of amino acid ionizable groups

Prentice Hall c2002

Chapter 3

27

pKa values of amino acid ionizable groups

Prentice Hall c2002

Chapter 3

28

Peptide Bonds Link Amino Acids in Proteins


Peptide bond - linkage between amino acids is a secondary amide bond Formed by condensation of the a-carboxyl of one amino acid with the a-amino of another amino acid (loss of H2O molecule) Primary structure - linear sequence of amino acids in a polypeptide or protein
Prentice Hall c2002 Chapter 3 29

Peptide bond between two amino acids

Prentice Hall c2002

Chapter 3

30

Polypeptide chain nomenclature


Amino acid residues compose peptide chains

Peptide chains are numbered from the N (amino) terminus to the C (carboxyl) terminus
Example: (N) Gly-Arg-Phe-Ala-Lys (C) (or GRFAK) Formation of peptide bonds eliminates the ionizable a-carboxyl and a-amino groups of the free amino acids
Prentice Hall c2002 Chapter 3 31

Aspartame an artificial sweetener

Prentice Hall c2002

Chapter 3

32

Amino Acid Composition of Proteins


Amino acid analysis - determination of the amino acid composition of a protein Peptide bonds are cleaved by acid hydrolysis (6M HCl, 110o, 16-72 hours)

Amino acids are separated chromatographically and quantitated


Phenylisothiocyanate (PITC) used to derivatize the amino acids prior to HPLC analysis
Prentice Hall c2002 Chapter 3 33

Acid-catalyzed hydrolysis of a peptide

Prentice Hall c2002

Chapter 3

34

Resonance structure of the peptide bond

Prentice Hall c2002

Chapter 3

35

Planar peptide groups in a polypeptide chain

Prentice Hall c2002

Chapter 3

36

Trans and cis conformations of a peptide group


Nearly all peptide groups in proteins are in the trans conformation

Prentice Hall c2002

Chapter 3

37

There Are Four Levels of Protein Structure


Primary structure - amino acid linear sequence

Secondary structure - regions of regularly repeating conformations of the peptide chain, such as a-helices and b-sheets Tertiary structure - describes the shape of the fully folded polypeptide chain
Quaternary structure - arrangement of two or more polypeptide chains into multisubunit molecule
Prentice Hall c2002 Chapter 3 38

a-helix

Prentice Hall c2002

Chapter 3

39

Stereo view of right-handed a helix


All side chains project outward from helix axis

Prentice Hall c2002

Chapter 3

40

Horse liver alcohol dehydrogenase


Amphipathic a helix (blue ribbon) Hydrophobic residues (blue) directed inward, hydrophilic (red) outward

Prentice Hall c2002

Chapter 3

41

b-Sheets (a) parallel, (b) antiparallel

Prentice Hall c2002

Chapter 3

42

Common motifs

Prentice Hall c2002

Chapter 3

43

Common domain folds

Prentice Hall c2002

Chapter 3

44

Quaternary structure of multidomain proteins

Prentice Hall c2002

Chapter 3

45

Quaternary Structure
Refers to the organization of subunits in a protein with multiple subunits (an oligomer) Subunits (may be identical or different) have a defined stoichiometry and arrangement

Subunits are held together by many weak, noncovalent interactions (hydrophobic, electrostatic)

Prentice Hall c2002

Chapter 3

46

Hemoglobin tetramer

(a) Human oxyhemoglobin (b) Tetramer schematic

Prentice Hall c2002

Chapter 3

47