LO: Discuss the structure and function of proteins

Proteins

• 96% of drug targets are proteins
• 100'000 proteins made from 20 amino acids
• Central carbon atom (C$\alpha$)
• Hydrogen atom
• Carboxyl group
• Amino group
• Side chain (variable)
• Chiral (stereoisomerism, D and L isomers) - except glycine, R chain is another H atom
• Arrangement around central C is asymmetric
• All amino acids are of the L configuration
• Amino acids divided into groups based on side chain properties: Non-polar, polar, positive (basic) and negative charge (Acidic)

Primary structure

• Order of amino acids
• From N (amine) to C (carboxyl)

Secondary structure

• Polypeptide chain folding due to chemical interactions between carboxyl and amino groups
• $\alpha$ helices - coiled
• $\beta$ pleated sheet - flat and wavy

Tertiary structure

• Overall fold of polypeptide
• Depends on the arrangement of secondary structures
• Folds can be stabilised by ionic, hydrogen, disulfide bonds or hydrophobic interactions

Quaternary structure

• More than one polypeptide chain
• Identical - same gene
• Different - more than one gene
• Arrangement of these chains is 4$\mathrm{°}$ structure
• Subunits cooperate to enable complex function

Modularity

• Complex proteins made up of 'domains'
• Domains - smaller folded regions with particular functions which can be assembled in different ways to make different final structures

Dynamic

• Intra and intermolecular bonds are dynamic - proteins can change shape rapidly
• Changes to protein structure can impair function which can lead to disease

Types

LO: Discuss the role of enzymes in catalysts and describe enzyme kinetics

Enzymes

• Catalysts - increase rate of chemical reactions but not changed, so reusable
• Most metabolic reactions would occur too slowly to keep cells functioning without enzymes
• Nearly all enzymes are proteins, small number are RNA
• Lowers activation energy so less energy needed to convert substrate to product
• Most are large globular proteins
• Active site that binds to specific substrate to catalyse reaction
• Important biomarkers

Roles

• Digestion
• Metabolism
• Cellular communication
• Cellular energy storage and delivery
• Movement
• Drug metabolism

Selectivity

• Shape of active site and substrate
• R groups of amino acids at interaction site
• Cofactors in active site

Lock and key

• Substrate - key
• Enzyme - lock
• Complementary so binds to catalyse

Induced fit

• Active site changes on substrate binding
• Helps to orient substrate correctly and strain bonds in substrate

Enzyme kinetics

• How enzymes accelerate reactions and the factors that affect it
• Substrate ^enzyme $\rightleftharpoons$_enzyme Product
• Amount of product against time graph:
• Graph plateaus due to running out of substrate, enzyme denaturation, product inhibition
• Linear part used to calculate initial rate of reaction

Enzyme activity

• Temperature (optimal 37$\mathrm{°}$C) - high temperatures lead to H bond disruption so 2$\mathrm{°}$ and 3$\mathrm{°}$ is lost
• pH (optimal 6-8) - Outside of range H bonds are disrupted causing denaturation
• Cofactors - helper molecules that interact with enzymes and required for their activity, can be inorganic ions or organic molecules
• Organic co-enzymes cannot be made so need to get them from our diet as vitamins

Inhibitors

Used to treat

• Pain
• Infections
• Cardiovascular disease
• Cancer

Mutations

• Can cause inherited diseases