Proteins: Structure and Function

Amino acids, building blocks of proteins

The peptide bond and other bonds

Protein folding

Hierarchy of protein structure

Domains and folds

Higher orders of organization

 Isoelectric Point (pI) of Amino Acids

1. The isoelectronic point or isoionic point is the pH at which the amino

acid does not migrate in an electric field.
2. This means it is the pH at which the amino acid is neutral, i.e. the zwitterion
form is dominant.
3. The pI is given by the average of the pKas that involve the zwitterion, i.e.
that give the boundaries to its existence.

pI = ½(pKa1 + pKa2)

pI = ½(pKa1 + pKa3)
The 22 Amino Acids Found in Living Systems
Families of Amino Acids
Families of Amino Acids
Families of Amino Acids
Peptide Bonds form the Backbone of Polypeptides
Torsional Angles in the Polypeptide Backbone

φ ψ
 The Ramachandran Plot

+180

-180 +180
φ
The Polypeptide Chain Forms the Primary Structure of the
Protein
Other Bonds that Contribute to Protein Structure
Folding of a Polypeptide Chain
a-helix and b-sheet
Parallel and Anti-parallel b-sheets
Coiled-coil Domain
Protein “folds” or Super-secondary Structures
Folds Generate Active Centres of Proteins

Active site of serine proteases

Protein Tertiary Structure: Domains
Distribution of Protein Domains
Quartenary Structure: Protein Subunit Interaction

Cro-repressor homodimer
Quartenary Structure: Protein Subunit Interaction

Neuraminidase homotetramer
Globular Proteins can Form Filamentous Structures that
Function as the Cell’s Structural Elements

Actin Microfilament
Extracellular Matrix Proteins are Fibrous Proteins

Collagen Triple-helix

Elastin Network
Protein Assemblies Form Cellular Structures
Protein Assemblies Give Rise to Elaborate Molecular Machines

Bacterial flagellar motor

Ligand-binding to the Active Site of a Protein

Ser

cAMP
Ser
Arg

Thr

Glu
Amino Acids in the Active Site are Highly Conserved
Presence of Unusually Reactive Amino Acids in Active Sites

The Catalytic Triad in Serine Proteases

Three ways in which Proteins Interact
Multiple Noncovalent Bonds Mediate Interactions between
Protein and Ligand
Enzymes are Protein Molecules that Function as Catalysts

Hydrolases - general term for enzymes that catalyze a hydrolytic cleavage reaction.
Nucleases - break down nucleic acids by hydrolyzing bonds between nucleotides.
Proteases - break down proteins by hydrolyzing bonds between amino acids.
Synthases - general name used for enzymes that synthesize molecules in anabolic
reactions by condensing two smaller molecules together.
Isomerases - catalyze the rearrangement of bonds within a single molecule.
Polymerases - catalyze polymerization reactions such as the synthesis of DNA and
RNA.
Kinases - catalyze the addition of phosphate groups to molecules. Protein kinases are
an important group of kinases that attach phosphate groups to proteins.
Phosphatases - catalyze the hydrolytic removal of a phosphate group from a molecule.
Oxido-Reductases - general name for enzymes that catalyze reactions in which one
molecule is oxidized while the other is reduced. Enzymes of this type are often called
oxidases, reductases, and dehydrogenases.
ATPases - hydrolyze ATP. Many proteins with a wide range of roles have an energy-
harnessing ATPase activity as part of their function, for example, motor proteins such
as myosin and membrane transport proteins such as the sodium–potassium pump.
Enzymes Decrease the Activation Energy and Stabilize
the Transition State

ΔG for the reaction