Protein Structure and Function

1
Chapter 3

• Protein Structure and Function

2
Outline

• Next 4 chapters address 4 major classes of
  biological molecules (proteins, nucleic acids,
  carbohydrates, lipids)
• Experiments in early chemical evolution
• Amino acid (AA) structure and nature
• Protein formation
• Protein structure and function
• Enzymes

3
Chemical Evolution

• Oparin and Haldane (1920s)
• first to propose idea of chemical evolution
• Theory of chemical evolution
• 1st molecules were small, C-containing compounds
  (i.e. H2CO and HCN)
• precursors such as H2CO and HCN form sugars, AA,
  and nitrogenous bases and eventually complex
  carbohydrates, proteins and nucleic acids
• prebiotic soup of AA (building blocks for
  proteins), sugars (building blocks for complex
  carbohydrates, nucleic acids (building blocks for
  DNA and RNA)
• single molecule acquires ability to
  self-replicate (end of chemical evolution,
  beginning of biological evolution)

4
Evidence for Chemical Evolution

• Miller spark and discharge experiment (1953)
• can complex organic cmpds be synthesized from
  simple molecules in environment similar to
  early Earth?
• reducing atmosphere
• NH3, H2, CH4, H2O vapor
• electric discharge created
  sparks
• deep red solution containing
  HCN, H2CO and AA
• YES

5
Evidence forChemical Evolution

• Now believe early atmosphere contained oxidized C
  (CO2, CO) not reduced (CH4)
• Miller Spark and Discharge expt wont work w/
  oxidized C
• Bar Nun and Chang experiments studied chemical
  evolution in oxidized atmosphere
• can sunlight trigger reduction of C from mixture
  of volcanic gases?
• water vapor, CO, CO2, H2, N2 exposed to high-S
  radiation
• variety of reduced-C cmpds (H2CO, acetaldehyde,
  CH4) form
• YES

6
Evidence of Chemical Evolution

• Wächtershäuser and Huber propose chem.
  evolution occurred at hydrothermal
  vents
• hydrothermal vents/black smokers
  intense
  pressure, 450C water
• superheated water dissolves iron,
  sulfur, nickel,
  and reduced C cmpds
  spewed out into 4C water
• methanethiol (CH3SH) produced
  
• can complex organic cmpds be
  synthesized at
  hydrothermal vents?
• CH3SH CO ? acetic acid
  (organic cmpd)
• YES

Black smoker
Mineral deposits
Ocean floor
Superheated water
Heat from magma below
7
Evidence for Chemical Evolution

• Other sources of precursors for life
• Murchison meteorite (1969) contained 18 different
  amino acids
• 100 kg found in Australia
• contains 92 AA (19 of which are found on Earth)
• interstellar dust contains HCN and aldehydes
• key in AA formation

8
Structure of Amino Acids

• Amino acids are monomers that are building blocks
  of proteins
• central C w/ 4 single bonds
• H, amino (NH2), carboxyl (COOH), R-group
• only left-handed AA isomers occur in organisms
• pH 7 causes ionization of COOH to COO and NH2 to
  NH3
• ? solubility and reactivity

9
Amino Acid R-Groups

• 20 AA identified by R-group
• side chains affect solubility and reactivity
• nonpolar R-groups lack charged/electronegative
  atoms (C, H only)
• hydrophobic, avoid water
• not very reactive
• chemical behavior depends on size/shape
• polar or acidic or basic R-groups contain
  charged/electronegative atoms (hydroxyl, amino,
  carboxyl)
• hydrophilic, disperse in water
• chemical behavior depends on reactivity

10
Sides Chains of Amino Acids
C and/or H based (nonpolar)
H
H
H
H
H
H
O
O
O
O
O
O
H3N
H2N
C
C
H3N
C
C
H3N
C
C
H3N
C
C
H3N
C
C
C
C
O
O
O
O
O
O
CH
CH2
CH
H3C
CH3
H
CH2
H2C
H3C
CH3
CH
CH2
CH2
CH3
H3C
CH3
Alanine (A) Ala
Isoleucine (I) Ile
Glycine (G) Gly
Valine (V) Val
Proline (P) Pro
Leucine (L) Leu
H
H
H
H
H
O
O
O
O
O
C
C
C
C
C
H3N
H3N
C
C
C
H3N
H3N
C
H3N
C
O
O
O
O
O
CH2
CH2
CH2
CH2
CH2
CH2
SH
NH
S
OH
CH3
Phenylalanine (F) Phe
Tyrosine (Y) Tyr
Methionine (M) Met
Cysteine (C) Cys
Tryptophan (W) Trp
Ring structures (polar and non)
Sulfur containing
11
Sides Chains of Amino Acids
Hydroxyl groups (polar)
Amino groups (polar)
H
H
H
H
O
O
O
O
C
H3N
C
C
C
C
C
C
H3N
H3N
H3N
C
O
O
O
O
CH
CH2
CH2
CH2
HO
OH
CH3
C
CH2
H2N
O
C
H2N
O
Serine (S) Ser
Threonine (T) Thr
Asparagine (N) Asn
Glutamine (Q) Gln
H
H
H
H
H
O
O
O
O
O
C
C
C
C
C
H3N
C
C
H3N
H3N
H3N
H3N
C
C
C
O
O
O
O
O
CH2
CH2
CH2
CH2
CH2
NH
CH2
C
CH2
CH2
O
O
NH
CH2
CH2
C
NH
O
O
CH2
NH3
C
NH2
NH2
Aspartate (D) Asp
Glutamate (E) Glu
Histidine (H) His
Lysine (K) Lys
Arginine (R) Arg
Basic (charged)
Acidic (charged)
12
Chirality
Hands are chiral

• Isomer same formula but different spatial
  arrangement
• optical isomers mirror- image molecules
• left- and right-handed forms
• only left-handed forms occur in organisms
• thalidomide tranquilizer given to pregnant women
  in 1950s in Europe
• one safe, other birth defects

Alanine is chiral, cannot be superimposed
CO2H
CO2H
H
CH3
H
NH2
CH3
NH2
CO2H
CO2H
Glycine is not chiral, can be superimposed
H
H
H
H
NH2
NH2
13
Polymerization of Monomers to Macromolecules

• Polymers (a.k.a. macromolecules) form by joining
  monomers (polymerization)
• AAs link together to form proteins
• linking of sugars complex carbohydrates
• linking of nucleotides nucleic acids

Monomer
Monomer
Polymer
Monomer
Monomer
Monomer
Monomer
Monomer
Monomer
Monomer
Polymerization (bonding together of monomers)
14
Polymerization

• Polymerization occurs by condensation/dehydration
  rxns
• condensation reactions removal of H2O joins 2
  monomers
• De-polymerization occurs by hydrolysis
• hydrolysis addition of H2O breaks polymer apart
• energetically favorable (? entropy, ? potential S)

OH
H
Water
Monomer
HO
H
Monomer
HO
HO
H
H
HO
HO
Monomer
H
H
H
Monomer

HO
OH

Water
H
15
Polymerization

• Hydrolysis dominates condensation in chemical
  equilibrium
• polymerization decreases entropy hydrolysis
  increases it
• polymers are less stable energetically than
  monomers
• Miller experiment - mineral clays necessary for
  polymerization of AA in prebiotic soup into
  macromolecules

16
Protein Structure

• 1 structure - AA linked by peptide bonds (btwn C
  and N of adjacent AA), 20n combinations
• flexible backbone, polar (unequal distribution of
  charges)
• single AA alter polypeptide folding and protein
  function (sickle cell)
• 2 structure - H-bonding btwn -COOH and -NH2 on
  different parts of same polypeptide backbone
• coiled ?-helix or folded ß-pleated sheets
• 3 structure - bonds btwn R-groups at different
  locations on same polypeptide
• additional folding into rods or globular masses
• 4 structure - multiple polypeptides interact to
  form single protein

17
Formation of peptide bond btwn 2 AAs
condensation rxn
H
O
H
H
H
H
O
O
O
H2N
C
H2N
C
C
H2N
C
C
C
N
C

H2O
C

OH
OH
OH
H
CH3
CH3
H
Peptide bond
Carboxyl group
Amino group
Polypeptide chain
N-terminus
C-terminus
H
H
H
H
H
H
O
O
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
N
C
C
N
N
C
C
C
C
N
C
C
N
C
C
C
C
N
C
N
C
C
OH
N
C
CH2
CH2
CH2
H
CH2
CH2
CH
CH3
CH3
H3C
OH
C
OH
SH
O
OH
H2N
Gly
Ala
Ser
Asp
Phe
Val
Tyr
Cys
COOH
8
2
1
3
5
4
6
7
18
R
R
H
H
O
OH
H
N
C
C
N
C
C
N
C
C
H-bonds btwn O of carboxyl and H of amino form
btwn peptide chains
O
H
O
H
H
H
R
H-bonds
O
H
R
H
O
H
C
C
N
C
C
N
C
C
N
HO
H
R
H
O
H
R
N
O
C
C
H
C
H
H
O
C
C
H
N
R
C
N
H
N
R
R
C
O
C
H
O
N
C
H
O
2 structures of proteins result from H-bonds
C
C
C
H
H
N
N
N
C
H
R
C
O
R
C
O
O
O
C
H
N
C
H
R
C
N
C
H
H
H
N
N
R
C
C
R
C
O
O
C
O
R
R
N
H
H
C
H
C
N
C
R
H
N
N
H
C
C
O
R
R
C
C
O
O
C
H
C
H
R
H
C
N
H
C
H
R
N
R
N
C
C
R
C
C
O
C
R
O
O
O
C
H
H
N
N
H
N
C
H
O
C
C
H
C
R
R
N
C
O
C
R
C
R
C
N
O
H
R
C
a-helix
b-pleated sheet
19
4 types of interactions btwn R-groups determine
3 structure of proteins
H bonds
H
O
C
N
btwn peptide groups
O
H3C
CH3
(CH2)4
CH2CH
NH3
CHCH2
O
CCCH2
H3C
CH3
OH
CH2
O
C
Ionic bond btwn full and opposing charges
btwn side chain and peptide group
van der Waals interactions weak attractions
btwn hydrophobic side chains
O
H
CH2
OH
CH2C
N
CH2
CH2
S
S
H
Disulfide bond covalent bond, strong
btwn 2 side chains
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21
Protein Folding and Function

• Protein function depends on shape
• Proper folding essential to normal functioning
• chaperones proteins that ensure proper folding
  (i.e. heat shock proteins)
• Denaturation unfolding of protein
• due to high temp.