Chapter 2 – Protein Structure and Function
2.1 The primary structure of proteins
The primary structure is the order in which individual amino acids
are linked together.
Peptide bonds are planar because of resonance structures.
Too much double bond character to rotate
Trans formation is more stable (usually)
2.2 The secondary structure of proteins
The secondary structure is regions of ordered structure adopted
by the protein chain.
(1) α-helix
Coiling of the protein in helix forms.
Caused by H-bonding.
(2) β-sheets
Layering of protein chains on top of each other.
H-bonding between peptide chains.
(3) β-turn
Allows the polypeptide chain to turn and go in opposite
direction.
2.3 The tertiary structure of proteins
The tertiary structure is the overall three-dimensional shape of a
protein.
This is crucial for the function of the protein and it’s
interaction with drugs.
Determined by the primary structure
Polymer is structured such that the reactions are
favourable.
2.5 Translation and post-translational modifications
Bonds that influence tertiary structure: Translation is the process by which a protein is synthesized in the
(1) Covalent bonds cell. During this, many proteins are modified.
Disulphide links
(2) Ionic or electrostatic bonds
Only a limited amount of amino acids is capable of ionic 2.6 Proteomics
bonds Genomics is the identification of the genetic code in humans and
(3) Hydrogen bonds other species.
Weak ionic interactions Proteomics is the research of identifying proteins in body-cells
(4) Van der Waals & hydrophobic interactions and how these interact with each other.
Most important type of interactions:
(1) Most opportunities for this type! 2.7 Protein function
(2) Proteins dissolved in water, so hydrophilic Several types of proteins can act as drugs target:
interactions on outside (with water), hydrophobic (1) Structural proteins
on the inside of the protein. Normally don’t act as drug target. Tubulin is a
Centre of protein hydrophobic! difference.
(2) Transport proteins
The active site protrudes into the centre of the protein. Can float freely within the cell membrane, because they
Must be more hydrophobic have hydrophilic residues on their outer surface which
Binding sites are also more hydrophobic than surface. interact with centre of cell membrane.
(3) Enzymes and receptors
Planar peptide bonds make the number of conformations Most important drug target!
restricted. (4) Miscellaneous proteins and protein interactions
Proteins interact with each other to produce a particular
2.4 The quaternary structure of proteins cellular effect.
The quaternary structure is the way in which the subunits
associate with each other.
Only for proteins that are made up of a number of
protein subunits.
, Chapter 3 - Enzymes: Structure & Function
3.1 Enzymes as catalysts
Enzymes are proteins which act as the body’s catalysts.
Speeds up the approach to equilibrium.
They lower the activation energy
Note:
(1) The substrate can (next to enzyme) also change shape to
maximize bonding interactions for example by bond
rotation.
(2) The bonding interactions can not be too strong, as that
would not allow the substrate to leave again.
Acid-base catalysis is important.
Provided by histidine with imidazole ring = weak base to
3.2 How do enzymes catalyse reactions? accept/donate protons. Glutamic acid = proton source,
Factors involved: aspartate = proton acceptor, aspartic acid = proton
(1) Enzymes provide a reaction surface & suitable donor, tyrosine = proton source.
environment
(2) Enzymes bring reactants together and position them Nucleophilic groups can also participate in mechanisms
correctly so that they easily attain their transition-state Serine (OH) and cysteine (SH) > forming intermediates
configurations Catalytic triad might be involved to make alcohol better
(3) Enzymes weaken bonds in the reactants nucleophile > other amino acids help to activate and
(4) Enzymes may participate in the mechanism orient the alcohol group of serine
(5) Enzymes form stronger interactions with the TS than Lysine can act as nucleophilic group in hydrophobic
with the substrate/product environment (otherwise protonated)
Substrates bind to, and react at, the active site of the enzyme. Cofactors = additional, non-protein substances required for the
reaction to take place.
Metal ions (zinc)
3.3 The active site of an enzyme Small organic molecules = coenzymes (NAD+, pyridoxal
Has to be on/near the surface of the enzyme, so substrate can phosphate) > bound by ionic bonds + other non-covalent
reach it.
bonds
Groove, hollow or gully in the surface.
Prosthetic groups: bound covalently coenzymes
Amino acids present in the binding site, can have 2 roles:
(1) Binding of the substrate or a cofactor in the active site. Names of enzymes depend on the type of reaction it catalyses.
(2) Catalytic; involved in the mechanism of the reaction. Oxidase: an enzyme that catalyses oxidation reactions
-ase means it is an enzyme
3.4 Substrate binding at an active site
Interactions are same as responsible for tertiary structure. Ionic Genetic polymorphism: DNA that codes for proteins is not equal
interactions are more important here! from person to person: 1 different base pair every 1000.
Binding regions are present within the active site, to take part in ‘Wrong’ amino-acids can be implemented in protein.
substrate binding. This can result in different function.
3.5 The catalytic role of enzymes 3.6 Regulation of enzymes
Enzymes catalyse reachtions by providing binding interactions, The regulation of enzymes is done by agents which can either
acid/base catalysis, nucleophilic groups and cofactors. In the enhance or inhibit catalytic activity.
Fischer’s Lock and Key-mechanism, the substrate fits perfectly These agents bind at allosteric binding site (other than
into the active site of the enzyme. active site) > where agents control activity of enzyme
Does not explain why some enzymes work on multiple bind
substrates as this mechanism keeps both enzyme and Why do these agents bind on separate site?
substrate rigid. (1) Feedback control; the final product controls its own
synthesis by inhibiting the first enzyme in the pathway.
Allosteric binding site must recognize the final product.
(2) Feedback control on same binding site would be less
efficient; product would have to compete with
substrate.
In the Koshland’s Induced-fit model, the substrate induces the But, regulation of enzymes can also be done by externally or by
active site to take up the ideal shape to accommodate it. proton-proton interactions.
2.1 The primary structure of proteins
The primary structure is the order in which individual amino acids
are linked together.
Peptide bonds are planar because of resonance structures.
Too much double bond character to rotate
Trans formation is more stable (usually)
2.2 The secondary structure of proteins
The secondary structure is regions of ordered structure adopted
by the protein chain.
(1) α-helix
Coiling of the protein in helix forms.
Caused by H-bonding.
(2) β-sheets
Layering of protein chains on top of each other.
H-bonding between peptide chains.
(3) β-turn
Allows the polypeptide chain to turn and go in opposite
direction.
2.3 The tertiary structure of proteins
The tertiary structure is the overall three-dimensional shape of a
protein.
This is crucial for the function of the protein and it’s
interaction with drugs.
Determined by the primary structure
Polymer is structured such that the reactions are
favourable.
2.5 Translation and post-translational modifications
Bonds that influence tertiary structure: Translation is the process by which a protein is synthesized in the
(1) Covalent bonds cell. During this, many proteins are modified.
Disulphide links
(2) Ionic or electrostatic bonds
Only a limited amount of amino acids is capable of ionic 2.6 Proteomics
bonds Genomics is the identification of the genetic code in humans and
(3) Hydrogen bonds other species.
Weak ionic interactions Proteomics is the research of identifying proteins in body-cells
(4) Van der Waals & hydrophobic interactions and how these interact with each other.
Most important type of interactions:
(1) Most opportunities for this type! 2.7 Protein function
(2) Proteins dissolved in water, so hydrophilic Several types of proteins can act as drugs target:
interactions on outside (with water), hydrophobic (1) Structural proteins
on the inside of the protein. Normally don’t act as drug target. Tubulin is a
Centre of protein hydrophobic! difference.
(2) Transport proteins
The active site protrudes into the centre of the protein. Can float freely within the cell membrane, because they
Must be more hydrophobic have hydrophilic residues on their outer surface which
Binding sites are also more hydrophobic than surface. interact with centre of cell membrane.
(3) Enzymes and receptors
Planar peptide bonds make the number of conformations Most important drug target!
restricted. (4) Miscellaneous proteins and protein interactions
Proteins interact with each other to produce a particular
2.4 The quaternary structure of proteins cellular effect.
The quaternary structure is the way in which the subunits
associate with each other.
Only for proteins that are made up of a number of
protein subunits.
, Chapter 3 - Enzymes: Structure & Function
3.1 Enzymes as catalysts
Enzymes are proteins which act as the body’s catalysts.
Speeds up the approach to equilibrium.
They lower the activation energy
Note:
(1) The substrate can (next to enzyme) also change shape to
maximize bonding interactions for example by bond
rotation.
(2) The bonding interactions can not be too strong, as that
would not allow the substrate to leave again.
Acid-base catalysis is important.
Provided by histidine with imidazole ring = weak base to
3.2 How do enzymes catalyse reactions? accept/donate protons. Glutamic acid = proton source,
Factors involved: aspartate = proton acceptor, aspartic acid = proton
(1) Enzymes provide a reaction surface & suitable donor, tyrosine = proton source.
environment
(2) Enzymes bring reactants together and position them Nucleophilic groups can also participate in mechanisms
correctly so that they easily attain their transition-state Serine (OH) and cysteine (SH) > forming intermediates
configurations Catalytic triad might be involved to make alcohol better
(3) Enzymes weaken bonds in the reactants nucleophile > other amino acids help to activate and
(4) Enzymes may participate in the mechanism orient the alcohol group of serine
(5) Enzymes form stronger interactions with the TS than Lysine can act as nucleophilic group in hydrophobic
with the substrate/product environment (otherwise protonated)
Substrates bind to, and react at, the active site of the enzyme. Cofactors = additional, non-protein substances required for the
reaction to take place.
Metal ions (zinc)
3.3 The active site of an enzyme Small organic molecules = coenzymes (NAD+, pyridoxal
Has to be on/near the surface of the enzyme, so substrate can phosphate) > bound by ionic bonds + other non-covalent
reach it.
bonds
Groove, hollow or gully in the surface.
Prosthetic groups: bound covalently coenzymes
Amino acids present in the binding site, can have 2 roles:
(1) Binding of the substrate or a cofactor in the active site. Names of enzymes depend on the type of reaction it catalyses.
(2) Catalytic; involved in the mechanism of the reaction. Oxidase: an enzyme that catalyses oxidation reactions
-ase means it is an enzyme
3.4 Substrate binding at an active site
Interactions are same as responsible for tertiary structure. Ionic Genetic polymorphism: DNA that codes for proteins is not equal
interactions are more important here! from person to person: 1 different base pair every 1000.
Binding regions are present within the active site, to take part in ‘Wrong’ amino-acids can be implemented in protein.
substrate binding. This can result in different function.
3.5 The catalytic role of enzymes 3.6 Regulation of enzymes
Enzymes catalyse reachtions by providing binding interactions, The regulation of enzymes is done by agents which can either
acid/base catalysis, nucleophilic groups and cofactors. In the enhance or inhibit catalytic activity.
Fischer’s Lock and Key-mechanism, the substrate fits perfectly These agents bind at allosteric binding site (other than
into the active site of the enzyme. active site) > where agents control activity of enzyme
Does not explain why some enzymes work on multiple bind
substrates as this mechanism keeps both enzyme and Why do these agents bind on separate site?
substrate rigid. (1) Feedback control; the final product controls its own
synthesis by inhibiting the first enzyme in the pathway.
Allosteric binding site must recognize the final product.
(2) Feedback control on same binding site would be less
efficient; product would have to compete with
substrate.
In the Koshland’s Induced-fit model, the substrate induces the But, regulation of enzymes can also be done by externally or by
active site to take up the ideal shape to accommodate it. proton-proton interactions.
