Protein Ramachandran Plot – φ(phi) angle of rotation,

ψ(psi) angle of rotation, co-planarity gives rise

Peptide Bond – the most important reaction of
to angle of rotations
amino acids is the formation of peptide bonds.

Peptide Bond – amide linkages formed when

the unshared electron pair of the α-amino
nitrogen atom of one amino acid attacks the α-
carboxyl carbon of another.

Dehydration reaction – removal of water

Peptide Bond – bonding between carbon and

nitrogen. O=C-N-H

Resonance Stabilization of the Peptide Bond –
strength of peptide bond, rotation.
Primary Structure – the amino acid sequence
determines the protein’s primary structure.
- The number and order of all amino acid
residues constitute the primary
structure of proteins.
- Pentapeptide (5 amino acid residues), 4
peptide bonds.
- Amino acids present in peptides are
called aminoacyl residues and are
named by replacing the -ate or -ine
suffixes of free amino acids with -yl (e.g.
alanyl, aspartyl, tyrosyl)
- Peptides are then named as derivatives
of the carboxyl terminal aminoacyl
residue.
Secondary Structure – the folding of short (3- to
30-residue), contiguous segments of
polypeptide intro geometrically ordered units.
α-helix – hydrogen bonds are responsible for
the helical structure; side chains are oriented
outwards.
- Hydrogen bonds (dotted lines) formed
between H and O atoms stabilize a
polypeptide in an α-helical
conformation.
β-pleated sheet – antiparallel (C-N and N-C),
parallel (same direction) depends on nitrogen
and carboxyl terminal with respect to the chain.
- Hydrogen bonds are responsible for the
geometric structure of amino acids.
β-turn – most common Type 1>Type 2 (Glycine
as third residue). Bond of 1st and 4th.
- Isomers – trans (most common, not
crowded), cis configurations
- Supersecondary structures

- Peptide bonds restrict possible

secondary conformations.
1. α-helix
a. right-handed
b. left-handed
2. β-pleated sheet
a. parallel
b. antiparallel
3. β-turns and α-loops
Tertiary Structure – the overall three-
dimensional (3D) arrangement of atoms in
proteins.
- Unique three-dimensional
conformations
- Globular proteins
- Native (biologically active) structures
Protein Folding – an unorganized, nascent
(newly synthesized) molecules acquires a highly
organized structure.
- Consequence of the interactions
between the side chains in their
primary structure.
Features
For Globular Proteins
1. Many polypeptides fold in such a
fashion that amino acid residues that
are distant from each other in the
primary structure come into close
proximity.
2. Because of efficient packing as the
polypeptide chain folds, globular
proteins are compact. During this
process, most water molecules are
excluded from the protein’s interior
making interactions between both polar
and nonpolar groups possible.
3. Large globular proteins (i.e., those with
more than 200 amino acid residues)
often contain several compact units
called domains. Domains are typically
structurally independent segments that
have specific functions (e.g., binding an
ion or small molecule).
Interactions
1. Hydrophobic interactions – as a
polypeptide folds, hydrophobic R
groups are brought into close proximity
because they are excluded from water.
2. Electrostatic interactions – the
strongest electrostatic interaction in
proteins occurs between ionic groups of
opposite change referred to as salt
bridges.
a. Salt bridges – noncovalent, in
regions of the protein where
water is excluded, energy
required to remove water
molecules from ionic groups
near the surface.
In proteins that consists of more than one
polypeptide chain, each polypeptide is called a
subunit.
Ligands – are molecules that bind to specific
sites on larger molecules such as proteins.
- Ligand binding pockets are water-
depleted regions of the protein. To
maximize binding.
3. Hydrogen bonds – a significant number
of hydrogen bonds form within a
protein’s interior and on its surface.
4. Covalent bonds – covalent linkages are
created by chemical reactions that alter
a polypeptide’s structure during or after
its synthesis. (ex. disulfide bridges)
In extracellular environments these strong
linkages partly protect protein structure from
adverse changes in pH or salt concentrations.
Intracellular proteins do not contain disulfide
bridges because of high cytoplasmic
concentrations of reducing agents.
The precise nature of the forces that promote
the folding of proteins has not yet been
completely resolved.
- It is clear, however, that protein folding
is a thermodynamically favorable
proves with an overall negative free
energy change.
Free Energy Equation – ΔG = ΔH – TΔS
- H (enthalpy), T (temperature), S
(entropy)
- A negative free energy change in a
process is the result of a balance
between favorable and unfavorable
enthalpy and entropy changes.
As a polypeptide folds, favorable (negative) ΔH
values are the result in part of the sequestration
of hydrophobic side chains within the interior of
the molecule and the optimization of other
noncovalent interactions.
- Opposing these factors is the
unfavorable decrease in entropy that
occurs as the disorganized polypeptide
folds into its highly organized native
state.
Tertiary Structure (Cont.)
Net free energy change between the folded and
unfolded state is relatively modest (the energy
equivalent of several hydrogen bonds).
Balance between favorable and unfavorable
forces, allows proteins the flexibility they
require for biological function.
Example
EF Hand – helix-loop-helix, binds with cation
Zinc finger – found in DNA binding proteins,
cysteine residues bind with zinc
Leucine zipper – DNA binding domain, knobs
represent leucine side chains
Quaternary Structure – defines the polypeptide
composition of a protein and for an oligomeric
protein, the spatial relationships between its
subunits or protomers (polypeptide).
- Many proteins, especially those with
high molecular weights, are composed
of several polypeptide chains.
- Each polypeptide component is called a
subunit. Subunits in a protein complex
may be identical or quite different.
- Multi-subunit proteins in which some or
all subunits are identical are referred to
as oligomers. Oligomers are composed
of protomers, which may consist of one
or more subunits.
- Oligomeric proteins – contain two or
four subunits protomers (Dimer,
tetramer)
Considerations
1. Synthesis of separate subunits may be
more efficient than substantially
increasing the length of a single
polypeptide chain.
2. In supramolecular complexes such as
collagen fibers, replacement of smaller
worn-out or damaged components can
be managed more effectively.
3. The complex interactions of multiple
subunits help regulate a protein’s
biological function.
Monomeric proteins – consist of a single
polypeptide chain.
Dimeric proteins – contain two polypeptide
chains.
Homodimers contain two copies of the same
polypeptide chain. In heterodimer, the
polypeptides differ.
Greek letters are used to distinguish different
subunits of a heterooligomeric protein, and
subscripts indicate the number of each subunit
type.
Representation
- X-ray diffraction, space-filling model