Lecture 3 Fall 2013

Office Hours: Mondays 1:30-3 PM

5301D MSRB III

Karina Kangas Office hours:
Tues 1-3 PM
Location TBA
Focus on the side chains
Be able to recognize the 20 amino acids
Learn the 3 letter and 1 letter abbreviations
Know their properties:

What about the amino acids do you need
to know?
Charged at acidic, neutral, or
basic pH?
Approx pKa of the side groups
Hydrophobic?
Aromatic
H-bonds?

2
3
Peptides and Proteins
Peptides - chemistry and
structure
Proteins - primary, secondary,
and tertiary structures
A peptide bond links two amino acids
The amine and carboxylate
groups of two amino acids
react to form a peptide bond
as a water molecule released.
This is an example of a
condensation reaction.
Peptide bonds
N-terminus C-terminus
A peptide bond
links two amino
acids
Leu-enkephalin opioid
peptide modulates pain
YGGFL 5
Biomedical Applications of Synthetic Peptides
Vasopressin A peptide hormone that
stimulates water absorption in the
kidney
1-Desamino-8-D-arginine vasopressin
synthetic analog of vasopressin
used as a drug
Aspartame: A Peptide Artificial Sweetener
Aspartame commercial name
NutraSweet.
Composed of Aspartate and the
methyl ester of Phenylalanine
Hydrolysis products: Aspartate,
Phenylalanine, and Methanol
Aspartame is believed to bind and
activate the T1R family of
sweetness receptors in the taste
buds.
Individuals with phenylketonuria
(PKU), a genetic defect in
metabolizing phenylalanine, must
avoid ingesting aspartame.
Cysteine side
groups can form
disulfide bonds
between peptide
chains of amino
acids
(e.g., insulin)

8
1.3
Bond distances are consistent with the
double bonded nature of peptide bond
9
1.0

1.24

Psi-Phi Angles
Voet and Voet, Wiley
10
Trans conformation of peptide bond is
favored for all amino acids except proline
11
Cis-Configuration is Only Observed in
Peptide Bonds Preceding Proline
Proline
Normally: cis :trans ~ 1:1000
Xaa-Pro: cis :trans ~ 1:3
12
MCDB310 Chapter 4: Protein
Structure
Slide
Courtesy of Ursula Jacob
Steric Hindrance when | = 60
and = 30
13
Although the peptide bond is planar, there
is rotation around the bonds to the alpha
carbon of each amino acid residue
14
The most favorable orientation of C bond
angles can be identified on a
Ramachandran diagram
15
16
Definitions of Protein Structure
Primary structure amino acid sequence
Secondary local conformation of peptide
backbone
Tertiary interaction of different secondary
structures on same polypeptide
Quaternary interaction of different polypeptides in
structure that has more than one protein component
Secondary Structure
Helices
|-strands and |sheets
Other (loops)
The alpha (( ) helix
The ( helix is a regularly repeating structure of amino
acids - 3.6 residues per turn and 5.4 A per turn

It was the first secondary structure proposed

All of the C=O and NH groups of the peptide bonds are
hydrogen bonded

Hydrogen bonding occurs between the I and I + 4s
residues in the helix

The ( helix is a right handed helix

All of the amino acid side chains are on the outside of the
helix
18
The ( helix
5.4
H-bonding All side chains (green
spheres) on outside
~3.6 residues per turn
N
C
Hydrogen bonding within the alpha helix
20
Hydrogen bond donor is the atom with H.
Hydrogen bond acceptor atom with electrons to share.
The ( helix
5.4
H-bonding
All side chains on
outside
21
An -Helix can be Amphipathic
Voet and Voet. Wiley
22
Alpha helices are accounted for in
the Ramachandran diagram
23
Ferritin is an example of a protein that is
almost completely alpha helical in structure
24
The ( helical coiled coil
The helical coiled coil is an example of quaternary
structure that is built solely on the a helical secondary
structure.

The coiled coil is commonly found in structural proteins
such as myosin, fibrin, keratin and intermediate filaments.
2
5
Part of the structure of hair keratin
Left-handed
superhelix
Voet and Voet, Wiley Irving Geis
26
o-Keratins - Crosslinked by Disulfide Bonds
27
MCDB310 Chapter 4:
Protein Structure
The collagen triple helix is stabilized by
repeated proline and hydroxyproline residues
Found in cartilage, ligaments, tendons, bones, teeth, skin, and blood vessels
28
Collagen
Several very unique features:
left-handed o-helix
3 AA per turn
3 o-chains are supertwisted
mainly Gly, Ala, Pro (Gly-X-Y
motif)
6% hydroxy-proline confers
thermostability (vitamin C
dependent synthesis scurvy!)

The pleated sheet (-sheet)
7
30
Antiparallel -sheet
Beta Sheet-
Antiparallel
7 A
31
The pleated sheet (parallel orientation)
32
sheets are depicted by arrows in
protein structure ribbon diagrams
3
3
Fatty Acid Binding Protein mCherry Fluorescent Protein
sheets often fold back upon
themselves to form barrels
34
The sheet
Each unit of the sheet is called a strand

Proteins often contain sheet or barrel structures

The strands may interact in parallel or antiparallel
orientations

Antiparallel strands are often connected by structures
called -turns

Side chains point in opposite directions
35
The turn
Residue i+1 is
often a proline
because it most
easily adopts the
required
conformation
36
Loops between alpha
helices or beta sheets
often are very
important functional
domains of proteins
37
Summary: Chapter 2.1-2.3
Amino acids know their names, three letter
abbreviations, structures, stereochemistry, and
side chain properties (please be familiar with the
one letter abbreviations for future readings in
Stryers Biochemistry)
Disulfide bonds
Primary structure: structure of the polypeptide
chain
Secondary structure: o-helices, |-sheets, and
loops

39 Slide from Ursula Jacob
Examples for Folding Motifs
2.4 - Tertiary protein structure
Globular (not fibrous) proteins have interior regions that are very hydrophobic and
important to protein stability. The surface of soluble proteins often contain charged
or polar residues.
The structure of globular
proteins is made up of
helices, strands,
turns as well as non-
repeating structures.
Cut-away view of interior Myoglobin
40
Protein Recognition
TBP
EcoR1
41
Domain structure of proteins
It is useful to think of proteins as containing discrete
domains whose conformation is mostly independent of
other domains in the protein
The domains are usually globular and consist of 100 to
400 amino acids that often fold independently
Often each domain is encoded by a distinct exon of a
gene
CD4; HIV binds it
42
An amazing protein, TG2 -
Transglutaminase 2
43
Cro protein
(dimer)
Hemoglobin
(tetramer of 2 ( and 2
subunits)
Quaternary Structure of Proteins
44
Protein Folding
45
Proteins Can Unfold in the Presence of Denaturants
(Urea and Guanidinium Chloride)
46
The transition between folded and unfolded
protein conformations is sharp (highly
cooperative)
47
48
Protein folding proceeds by progressively
stabilizing correct interactions between
amino acids