SCHOOL OF MATHEMATICAL AND NATURAL SCIENCES

BIOCHEMISTRY DEPARTMENT

Protein Biochemistry
BCM 3521

Lecturer: Dr. A. Burger

 20 Amino Acids

Nonpolar,
hydrophobic

Polar, uncharged

Polar, charged
Amino Acid Classification

aliphatic
G P
beta-branched
CS-S A
CH S N
V
L
I T D
Q
E
negative
M K
F Y H R
aromatic W
positive
hydrophobic charged
polar
Bioinformatics Methods II, Spring 2003

Venn diagram
relationship of the 20 naturally occurring amino acids to a selection of physio-
chemical properties thought to be important in the determination of protein
structure
Amino acid structure
Peptide bond formation 2-4
Resonance of the peptide unit
The amide structure has two resonance contributors:

• Because the bond between the carbonyl carbon and the nitrogen has a
partial double bond character, rotation around this bond is restricted
• Thus, the peptide unit is a planar, rigid structure and rotation in the
peptide backbone is restricted to the bonds involving the a carbon:
Secondary Structure
The atoms of the peptide bond lie in a plane
• The resonance stabilization energy of the planar structure
is 88 kJ/mol
• A twist about the C-N bond involves a twist energy of 88
kJ/mol times the square of the twist angle.
• Twists can occur about either of the bonds linking the
alpha carbon to the other atoms of the peptide backbone
Consequences of the Amide Plane
Two degrees of freedom per residue for the peptide chain

• Angle about the C(alpha)-N bond is denoted phi

• Angle about the C(alpha)-C bond is denoted psi
• The entire path of the peptide backbone is known if all phi and
psi angles are specified
• Some values of phi and psi are more likely than others.
The angles phi and
psi are shown here
 Protein backbone torsion angles

Ramachandran plot

Repeating values of phi ~-57o and

psi ~-47o give a right-handed
helical fold (the alpha-helix)
(in cytochrome C-256)
Steric Constraints on phi & psi
Unfavorable orbital overlap precludes some combinations of phi and psi

• phi = 0, psi = 180 is unfavorable

• phi = 180, psi = 0 is unfavorable
• phi = 0, psi = 0 is unfavorable
Steric Constraints on phi & psi
• G. N. Ramachandran was the first to demonstrate the convenience of
plotting phi, psi combinations from known protein structures
• The sterically favorable combinations are the basis for preferred
secondary structures
 2-5

The peptide bond

Ri+1

Ri
Phi (Φ) and Psi (ψ) angles can vary;
R=side chain their rotation allows polypeptides
O=C-N-H is planar to adopt their various structures
(double-bond character) (alpha-helices, beta-sheets, etc.)

cis conformation is rare except for proline

potential for steric hindrance

 2-6

Protein structure: overview

Structural element Description
primary structure amino acid sequence of protein
secondary structure helices, sheets, turns/loops
super-secondary structure association of secondary structures
domain self-contained structural unit
tertiary structure folded structure of whole protein
• includes disulfide bonds
quaternary structure assembled complex (oligomer)
• homo-oligomeric (1 protein type)
• hetero-oligomeric (>1 type)
Classes of Secondary Structure
All these are local structures that are stabilized by
hydrogen bonds
• Alpha helix
• Other helices
• Beta sheet (composed of "beta strands")
• Tight turns (aka beta turns or beta bends)
• Beta bulge
Protein secondary structures

Local structures which are typically recognized by specific

backbone torsion angles and specific mainchain hydrogen bond
pairing patterns
The Alpha Helix
Know these numbers
• Residues per turn: 3.6
• Rise per residue: 1.5 Angstroms
• Rise per turn (pitch): 3.6 x 1.5A = 5.4 Angstroms
• The backbone loop that is closed by any H-bond in an
alpha helix contains 13 atoms
• phi = -60 degrees, psi = -45 degrees
• The non-integral number of residues per turn was a
surprise to crystallographers
Alpha Helix
 2-7

Protein structure: helices

alpha 3.10 pi - alpha helices are about
10 residues on average
- side chains are well
staggered, preventing
steric hindrance
- helices can form
bundles, coiled coils, etc.

H-bonding

amino acids
per turn: 3.6 3.0 4.4

frequency ~97% ~3% rare

The Beta-Pleated Sheet
Composed of beta strands
• Also first postulated by Pauling and Corey, 1951
• Strands may be parallel or antiparallel
• Rise per residue:
•

• 3.47 Angstroms for antiparallel strands

• 3.25 Angstroms for parallel strands
• Each strand of a beta sheet may be pictured as a
helix with two residues per turn
 2-8

Protein structure: sheets

- the basic unit of a
beta-sheet is called a
beta-strand
- unlike alpha-helix, sheets
can be formed from
discontinuous regions of a
polypeptide chain
parallel
- beta-sheets can form
various higher-level
structures, such as a
beta-barrel
‘twisted’

Green
anti-parallel Fluorescent
Protein
(GFP)
 2-9

Protein structure: sheets (detail)

- notice the difference

in H-bonding pattern
between parallel and
anti-parallel beta-sheets

- also notice orientation

of side chains relative
to the sheets

‘twisted’
 2-10

Protein structure: turns/loops

alpha-helix beta-sheet

- there are various types of

turns, differing in the
number of residues and
H-bonding pattern
- loops are typically longer;
they are often called coils
and do not have a ribonuclease A
‘regular’
or repeating, structure loop
(usually exposed on surface)