Download Chap.21_Proteins, part 1

Chapter 21
Proteins
4/15/09
Spider Silk, a fibrous protein. . .tough on bugs
Not on you. . .(soft and smooth)
Proteins
• Proteins many have functions:
•1.Structure: collagen and keratin are the chief constituents of skin,
bone, hair, and nails.
•2. Catalysts: virtually all reactions in living systems are catalyzed by
•proteins called enzymes.
•3. Movement: muscles are made up of proteins called myosin and actin.
•4. Transport: hemoglobin transports oxygen from the lungs to cells;
other proteins transport molecules across cell membranes.
•5. Hormones: many hormones are proteins, among them insulin,
•oxytocin, and human growth hormone.
Proteins
6. Protection: blood clotting involves the protein fibrinogen;
the body used proteins called antibodies to fight disease.
7. Storage: casein in milk and ovalbumin in eggs store nutrients
for newborn infants and birds; ferritin, a protein in the liver,
stores iron.
8. Regulation: certain proteins not only control the expression
of genes, but also control when gene expression takes place.
Proteins are divided into two types:
1. fibrous proteins (e.g. collagen, keratin)
2. globular proteins (e.g. Hemoglobin)
Amino Acids  proteins
•A.A.s contains amino group, carboxyl group, R group.
R- group polarity
Most imp.
In Nature 20 alpha Amino acids exist (see table 21.1) :
AKA α A.A.s b/c amino group is on the α carbon
Chirality of Amino Acids
•Except glycine, all protein-derived amino acids have at least one
stereocenter (the α-carbon) and are chiral.
COO
COO+
H H NH
N3H3 +
CH
CH
3 3
D-Alanine
D-Alanine
COO
COO+ +
H 3HN3 N
HH
CH
CH
3 3
L-Alanine
L-Alanine
(Fischer
projections)
(Fischer
projections)
•In Nature majority of protein-derived α-amino acids are in the L-form.
•How do we know when/where it’s L vs D?
NH3 on the “Left” in Fischer proj.
Chirality of Amino Acids
• A comparison of the stereochemistry of L-alanine
and D-glyceraldehyde (as Fischer projections):
-
-
COO
H
NH3 +
COO
+
H3 N
CH3
D-A lanine
H
OH
CH2 OH
D -Glycerald ehyde
H
CH3
L-Alan ine
CHO
the n aturally
occu rring form
the n aturally
occu rring form
CHO
HO
H
CH2 OH
L-Glycerald ehyde
See table 21.1
R-group polarity  classification:
1.Nonpolar (hydrophobic-repel H2O
2. Polar (hydrophillic)
3. Basic (hydrophillic)
4. Acidic (hydrophillic)
Determines structure + function of protein
20 Protein-Derived AA
Red = R Groups, AKA Side Chains
Nonpolar side chains (at pH 7.0)
COO- A lanine
(A la, A)
+
NH3
COONH3
+
Glycine
(Gly, G)
-
+
COO
NH3 +
S
COONH3 +
Leucin e
(Leu, L)
Meth ion in e
(Met, M)
H
-
COO
Isoleucin e
(Ile, I)
-
-
COO
N
H
COO
NH3
COO- Phen ylalan ine
(Phe, F)
+
NH3
N
H
NH3
+
Prolin e
(Pro, P)
Tryptoph an
(Trp , W)
COO- Valine
(Val, V)
+
NH3
20 Protein-Derived AA
• Polar side chains (at pH 7.0)
COO-
H2 N
O
NH3 +
-
As paragine
(As n, N )
COO
HS
NH3
O
-
H2 N
COO
NH3
Glutamine
(Gln, Q)
+
HO
NH3
+
COO-
HO
NH3
+
Serine
(Ser, S)
OH
-
COO
+
Cysteine
(Cys, C)
Tyrosine
(Tyr, Y)
COO- Threon in e
(Thr, T)
NH3 +
Red = R Groups, AKA Side Chains
20 Protein-Derived AA
• Acidic and basic side chains (at pH 7.0)
-
COO-
O
O
NH3
As partic acid
(As p, D )
+
NH2 +
H2 N
O
-
COO
N
H
NH3
+
Arginin e
(Arg, R)
-
-
O
COO Glutamic acid
+
(Glu, E)
NH
N
3
N
H
+
H3 N
COONH3
Histidine
(His , H)
+
-
COO
NH3
+
Red = R Groups, AKA Side Chains
Lysine
(Lys, K)
Zwitterions – molecules that have:
• + charge on one atom
• - charge on another atom
Although amino acids commonly written in the un-ionized form,
they are more properly written in the zwitterion (internal salt) form.
O
R-CH-COH
NH2
Un-ionized
form
O
R-CH-CO+
NH3
Zwitterion
COOH (Acid) donates H+ to NH2 (base)
Zwitterions
ADD acid (decrease pH) what happens?
ADD base (increase pH) what happens?
When A.A.s have equal + & - charges
aka: isoelectric point (pI)
Ionization vs pH
• The net charge on an amino acid depends on the
pH of the solution in which it is dissolved.
• If we dissolve an amino acid in water, it is present in
the aqueous solution as its zwitterion.
•to summarize:
O
+
H3 N-CH-C-OH
R
pH 2.0
Net charge +1
OH
+
H3 O
O
+
H3 N-CH-C-O
R
pH 5.0 - 6.0
Net charge 0
OHH3 O+
O
H2 N-CH-C-OR
pH 10.0
N et ch arge -1
Isoelectric Point
• Isoelectric
point, pI:
The pH at
which the
majority of
molecules of
a compound
in solution
have no net
charge.
Nonpolar &
polar side chains
alanine
asparagine
cys teine
glutamine
glycine
isoleucine
leucine
methionine
phenylalanine
proline
serine
threonine
tyros ine
tryptophan
valine
pI
6.01
5.41
5.07
5.65
5.97
6.02
6.02
5.74
5.48
6.48
5.68
5.87
5.66
5.89
5.97
Acidic
Side Chains
aspartic acid
glutamic acid
Bas ic
Side Chains
arginine
histidine
lysine
pI
2.77
3.22
pI
10.76
7.59
9.74
Cysteine
• The -SH (sulfhydryl) group of cysteine is easily
oxidized to an -S-S- (disulfide).
+
2 H3 N-CH-COOCH2
SH
Cysteine
oxidation
reduction
+
H3 N-CH-COO
CH2
a disulfide
bon d
S
S
CH2
+
H3 N-CH-COO
Cystine
Peptides and Proteins
• Formation of an amide
H2O
The Peptide bond
Peptide named starting @ N-terminus
(e.g. Gly-Ala, see Table 21.1)
Peptides
• 1902, Emil Fischer proposed proteins are long
chains of amino acids joined by amide bonds.
• peptide bond: amide bond between the -carboxyl group of one
amino acid and the -amino group of another.
peptide
bond
CH3
+
H 3N
O-
O
Alanine (Ala)
+
+
H 3N
O
OCH2 OH
Serine (Ser)
CH3 H
O
+
N α
H 3N
O - + H2 O
O
CH2 OH
Alanyls erine
(Ala-Ser)
Writing Peptides
•Start at left, beginning with the free -NH3+ group and
ending with the free -COO- group on the right.
•C-terminal amino acid: the amino acid at the end of the
chain having the free -COO- group.
•N-terminal amino acid: the amino acid at the end of the
•chain having the free -NH3+ group.
+
H 3N
N-terminal
amino acid
O
C6 H5
O
H
N
N
OH
O
OH
COOSer-Phe-Asp
C-terminal
amino acid
Peptides and Proteins
• What would this tri-peptide be called?
Note: short chain A.A.s = peptides
Longer chained 10-20 A.A.s = polypeptides
> 30 A.A. chains = proteins (residues)
Other Amino Acids
• Hydroxylation (oxidation) of proline, lysine, and
tyrosine, and iodination for tyrosine, give these
nonstandard amino acids.
O
HO
C-O N
H 3N C H
COO-
H H
Hydroxyproline
I
I
O
+
H 3N
OH
COO-
N H3 +
Hydroxylysine
I
OH
Thyroxine
I
Properties of peptides and proteins
Note: R groups = AKA Side chains
(See table 21.1, previous slides)
1. determine Chem. + phys. Properties
 acid base behavior = most imp.
Know Which A.A.s:
polar?
Non polar?
basic? acidic?
~ by LOOKING @ R-group
Determine the chemical nature of these A.A.s
(i.e. R groups as Polar, Non polar, Basic or Acidic)
serine
Tryptophan
Glutamic acid
lysine
Which is the only A.A. that forms di-sulfide bonds?
Peptides and Proteins
• Proteins behave as zwitterions.
• Proteins isoelectric point, pI.
• At its pI, the protein has no net charge.
• At higher pH (more basic) than its pI, has net (-)charge.
• At lower pH (more acidic) than its pI, has net (+)charge.
• Hemoglobin, almost equal number of acidic and basic
side chains; its pI is 6.8. ~ 7
• Serum albumin has acidic side chains; its pI is 4.9.
• Proteins are least soluble in water at their isoelectric points and
can be precipitated from solution at this pH.
Changing the pH changes “the Nature” of Protein,)
Denaturing a Protein
Isoelectric point (pI)
neutral
Acidic solut.
pH 2
(protonated)
basic solut.
pH 10
(deprotonated)
NOTE: form/shape changes w/ pH change
Levels of Structure
• Primary structure:
the sequence of amino acids in a polypeptide
chain; read from the N-terminal amino acid to the C-terminal amino acid.
• Secondary structure:
conformations of amino acids in localized
regions of a polypeptide chain; examples are -helix, b-pleated sheet, and
random coil.
• Tertiary structure:
the complete three-dimensional arrangement of
atoms of a polypeptide chain.
• Quaternary structure:
the spatial relationship and interactions
between subunits in a protein that has more than one polypeptide chain.
» See Hemoglobin next slide. . .
Structure(s)
of Proteins