This lecture discusses protein structure and function, specifically focusing on secondary structure elements. It covers the conformations of peptide groups including cis and trans conformations, and dihedral angles phi and psi. Common secondary structures like alpha helices, beta sheets, and turns are described in detail. Alpha helices are stabilized by hydrogen bonds between amino acids four residues apart in the sequence. Beta sheets can be antiparallel or parallel depending on the direction of hydrogen bonding between strands. Turns and loops allow changes in the peptide chain direction. Amino acids have different preferences for forming these secondary structures.

1. HBC1011 Biochemistry I
Trimester I, 2018/2019
Lecture 7 – Protein structure and
function
Ng Chong Han, PhD
MNAR1010, 06-2523751
chng@mmu.edu.my
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2. Overview
• Conformation of the peptide group
• Secondary structures
– Alpha helix
– Beta sheet
– Turns and loops
2

3. The conformation of the peptide group
• The structure of peptides are flexible and yet
conformationally restricted
• Geometry of protein backbone:
– peptide bond is essentially planar
– 6 atoms lie in the same plane
• Nature of the chemical bonding:
– peptide bond has considerable double-bond character, it
is restricted to one of two possible conformations, either
trans or cis.
– constrains the conformation of the peptide backbone and
accounts for the bond's planarity.
3

4. Peptide Bonds Are Planar. In a pair of linked amino acids, six atoms (Cα, C, O, N, H,
and Cα) lie in a plane. Side chains are shown as green balls.
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2
3
4
5
6
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5. Cis and trans conformations
• Two conformations are possible for a planar peptide bond.
• Trans conformation: 2 α-carbon atoms are on opposite
sides of the peptide bond.
• Cis conformation: these groups are on the same side of the
peptide bond.
• Almost all peptide bonds in proteins are trans because cis
conformation create more steric hindrance between the
side chains attached to the two α-carbon atoms, making
them energetically unfavorable.
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6. Cis and trans conformations
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The trans form is strongly favored because of steric clashes
that occur in the cis form.
Green: side chain

7. Dihedral angles
• Two dihedral angles in
the peptide bond
determine the local
shape assumed by the
protein backbone.
• Bonds between the
amino group and the
α-carbon atom and
between the α-carbon
atom and the carbonyl
group are pure single
bonds.
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8. Dihedral angles
• The two adjacent rigid
peptide units may
rotate about these
bonds, taking on
various orientations.
• This freedom of
rotation about two
bonds of each amino
acid allows proteins to
fold in many different
ways.
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9. Dihedral angles
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• The rotations about these bonds can be specified by dihedral angles.
• The angle of rotation about the bond between the nitrogen and the
𝛂-atoms is called phi (𝛟).
• The angle of rotation about the bond between the 𝛂-carbon and the
carbonyl carbon atoms is called psi (𝛙).
• A clockwise rotation about either bond as viewed from the front of
the back group corresponds to a positive value.
• The 𝛟 and 𝛙 angles determine the path of the polypeptide chain.

10. Ramachandran diagram
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Are all combination of 𝛟 and 𝛙 possible?
G. N. Ramachandran recognized that many combinations are
forbidden because of steric collisions between atoms. The values
can be visualized on a 2D plot called Ramachandran diagram.
Three-quarters of the possible (𝛟 and 𝛙) combinations are
excluded simply by local steric clashes.
The most favorable regions are
shown in dark green; borderline
regions are shown in light
green. The structure on the
right is disfavored because of
steric clashes.

11. 11

12. Secondary structure
• Protein secondary structure can be described by the hydrogen-
bonding pattern of the peptide backbone of the protein.
• The most common 2nd structures: alpha (α) helices and beta (β)
sheets/beta strands
• Other 2nd structures: β turn, omega (Ω) loop
• Alpha helices, beta strands and turns are formed by a regular
pattern of hydrogen bonds between the peptide N-H and C=O
groups of amino acids that near each one another in the linear
sequence.
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13. • Linus Carl Pauling (February 28, 1901 –
August 19, 1994): American quantum chemist
and biochemist.
• Two Nobel prizes winner
• Awarded the Nobel Prize in chemistry for his
work describing the nature of chemical bonds.
The elucidation of the structure
of the α-helix is a landmark in
biochemistry because it
demonstrated that the
conformation of a polypeptide
chain can be predicted if the
properties of its components
are rigorously and precisely
known. 13

14. Alpha-helix
• A coiled rod-like
backbone structure forms
the inner part of the rod
and the side chains
extend outward in a
helical array.
• The α-helix is stabilized
by intrachain hydrogen
bonds (intra-strand)
between the NH and CO
groups of the main chain.
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15. Alpha-helix
Hydrogen-Bonding Scheme for an α-helix. In the α
helix, the CO group of residue n forms a hydrogen
bond with the NH group of residue n+ 4.
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16. Alpha-helix
• Each residue is related to the next one by
a rise of 1.5 Å (angstrom, 1Å = 0.1nm)
along the helix axis and a rotation of 100º,
which gives 3.6 amino acid residues per
turn of helix.
• Amino acids spaced three and four apart
in the sequence are spatially quite close to
one another in an α-helix.
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17. Alpha-helix
• The Ramachandran diagram (for
visualization of dihedral angles)
reveals that both right-handed
and the left handed helices are
possible conformations.
• However, essentially all α helices
in proteins are right-handed.
• Right-handed helices are
energetically more favorable
because there is less steric clash
between the side chains and the
backbone.
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18. Schematic Views of α-Helices. (A) A ball-and-stick model. (B) A ribbon
depiction. (C) A cylindrical depiction. 18

19. A Largely α-Helical Protein. Ferritin, an iron-storage protein,
is built from a bundle of α helices.
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20. Beta structure : beta strand
• β structure : β strands and β sheets
• A polypeptide chain, called a β strand is almost fully
extended rather than being tightly coiled as in the α helix.
• Beta sheet are stabilized by hydrogen bonding between
polypeptide strands (inter-strand).
• The distance between adjacent amino acids along a β
strand is approximately 3.5 Å
• The side chains of adjacent amino acids point in opposite
directions.
• β strands are rare because they are conformationally less
stable. However, when two adjacent β strands line up they
can form hydrogen bonds. This creates a β sheet.
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21. Structure of a β-Strand. The side chains are alternately
above and below the plane of the strand.
7 Å
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22. Beta sheet - Antiparallel
• When multiple β strands are arranged side-by-side, they
form β sheets.
• Adjacent chains in a β sheet can run in opposite
directions (antiparallel β sheet) or in the same direction
(parallel β sheet).
• Antiparallel arrangement: NH group & CO group of each
amino acid are respectively hydrogen bonded to the CO
group and the NH group of a partner on the adjacent
chain
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23. An Antiparallel β Sheet. Adjacent β strands run in opposite directions.
Hydrogen bonds between NH and CO groups connect each amino acid to a
single amino acid on an adjacent strand, stabilizing the structure. The
hydrogen bonds are essentially perpendicular to the β strands, and the
space in between is alternately wide and narrow.
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24. Beta sheet - Parallel
• Parallel arrangement: for each amino acid, the NH group is
hydrogen bonded to the CO group of one amino acid on
the adjacent strand, whereas the CO group is H-bonded to
the NH group on the amino acid two residues farther along
the chain.
• Parallel sheets are less stable than antiparallel sheet,
possibly because the hydrogen bonds are distorted.
• Many strands, typically 4 or 5 but as many as 10 or more,
can come together in β sheets. Such β sheets can be
purely antiparallel, purely parallel, or mixed.
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25. A Parallel β Sheet. Adjacent β strands run in the same direction.
Hydrogen bonds connect each amino acid on one strand with two
different amino acids on the adjacent strand. The hydrogen bonds are
evenly spaced but slanted.
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26. Structure of a Mixed β Sheet 26

27. Beta sheet
• In schematic diagrams: depicted by broad arrows pointing
in the direction of the carboxyl-terminal end to indicate the
type of β sheet.
• can be relatively flat but most adopt a somewhat twisted
shape.
• important structural element in many proteins. i.e.: fatty
acid-binding proteins, important for lipid metabolism, are
built almost entirely from β sheets
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28. A Twisted β Sheet. (A) A ball-and-stick model. (B) A schematic model. (C)
The schematic view rotated by 90 degrees to illustrate the twist more
clearly. 28

29. A Protein Rich in β Sheets.
The structure of a fatty acid-
binding protein.
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30. Polypeptide chains can change
direction by making reverse turns & loops
• Most proteins required reversals in the direction of their
polypeptide chains.
• Reversals: reverse turn (also known as the β turn or hairpin
bend)
• Reverse turns: CO group of residue i of a polypeptide is H-
bonded to the NH group of residue i + 3.
• This interaction stabilizes abrupt changes in direction of the
polypeptide chain.
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31. Structure of a
Reverse Turn.
The CO group of
residue i of the
polypeptide chain is
hydrogen bonded to
the NH group of
residue i + 3 to
stabilize the turn.
H bond stabilizes
the bend.
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32. Loops
• Unlike α helices and β strands, loops do not have regular,
periodic structures.
• Nonetheless, loop structures are often rigid and well
defined.
• Turns and loops invariably lie on the surfaces of proteins:
often participate in interactions between proteins & other
molecules.
• secondary structure: α helices, β strands, and turns along a
protein chain.
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33. Loops on a Protein Surface.
A part of an antibody molecule
has surface loops that mediate
interactions with other
molecules.
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34. Amino acid have different propensities for
forming α helices, β sheets and turns
• Amino acids vary in their ability to form 2nd structure
elements.
• Proline and glycine are sometimes known as "helix
breakers" because they disrupt the regularity of the α
helical backbone conformation.
• Alanine, glutamate, and leucine: α helices
• Valine & isoleucine: β strands.
• Glycine, asparagine, and proline: turns
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35. 35
Amino acid
preference:
secondary
structure