Proteins

Hydrolysis

peptide bonds, rigid and planar

• Building blocks from which cells are assembled • Constitute 2nd most present element of the cells • Composed of oxygen, hydrogen, carbon and nitrogen

• Structural proteins = provide mechanical support to cells and tissues • Enzymes = catalyse covalent bond breakage and formation • Transport proteins = carry small molecules or ions • Storage proteins = store small molecules or ions • Motor proteins = generate movement in the cells and tissues • Signal proteins = carry signals from cell to cell • Receptor proteins = detect signals and transmit them to the cells response machinery • Gene regulatory proteins = bind to DNA to switch genes on or off

All amino acids are built around a central carbon atom (α carbon or Cα) The side chain is the only feature that changes in amino acids There are approx 20 amino acids

• Proteins assembled from 20 amino acids - different chemical properties • Chain of amino acids joined by covalent peptide bond (condensation reaction)

in order to break the monomers, water is added into the amino acid (this is one of the ways food is digested)

N - terminus: amino group (NH3+ or NH2) and C - terminus: carboxyl group (COO- or COOH)

Amino Acid R groups influence protein structure and Amino acid side chains (R groups) give proteins their unique properties

pKa is the pH in which 50% of the molecules are in each of the following states By adding a base, we are then slowly removing hydrogen from the solution, which leads to the amino acid having no charge.

PI is the pH where the amino acid has no net electrical charge or is neutral

makes a gradient of pH, therefore the molecules will only migrate whilst it has a charge, so when it reaches its pI it will stop. It’s migrated not only by weight but also pI - in which we will obtain 2D electrophoresis.

A pH gradient is established by allowing a mixture of organic acids and bases (ampholytes) . Proteins migrates until it reaches pH that matches the pI

• Folding of proteins is influenced by peptide bond (it’s rigid) • Puts important constraints on polypeptide folding • Has two important characteristics = C-N bond inflexible (which limits folding) and asymmetry of charge favours hydrogen bonding within protein and other molecules • Peptide bond is rigid and planar • Adjacent atoms (α carbons of adjacent amino acids not free to rotate - as they are planar, which restrains on how many different forms can twist a given chain)

when proteins lose their side chain interactions

• Weak non-covalent bond between the electronegative atom (N or O) and H atom bound to another electronegative atom - polarity created, because the hydrogen is attracting the electrons (negative). • Individually weak but strong when in large numbers

Charged groups repel the same charge and attract opposite charge • Strong interaction - influence over greater distance • Non-directional unlike covalent bonds (limited to discrete angles) • Rely on both groups remaining charged - disrupted if change pH (denaturation at high or low pH) • They don’t need to glued together to make an unbreakable bond

• Attracting/repelling forces between transient positive and negative charges in non-polar molecules • Momentary asymmetries in electron distribution = each interaction is transient and weak, only effective in short distances and has an important role especially in holding proteins that fit together in position • Strength of Van der Waals interaction decreases rapidly with increasing distance = only effective when close together • Weaker than typical hydrogen bond • Important for the structure of proteins and binding together of 2 molecules with complementary surfaces

• Weak force - central role in determining protein shape • Water forces hydrophobic groups together - minimise disruptive effect on H-bonded network of surrounding water molecules • Distribution of polar and non-polar (hydrophobic) amino acids affects folding of protein - the water will push the molecules to the same place (hydrophilic faces the outside and hydrophobic faces the inside - different in the membrane)

Disulphide bond is a covalent chemical bond between two sulphur atoms from side chains of Cys

• Final folded structure - conformation of protein = which is determined by energetic considerations - free energy is minimal • Proteins folding can be studied - denatures protein often (not always) recover natural shape • Each protein folds into a single stable conformation - may change slightly if interacts with molecules - crucial for function • If protein folds incorrectly - forms aggregates. misfolded proteins can contribute to disease • Can fold without help but often assisted by chaperone proteins • Chaperones make folding more efficient and reliable

• Primary • Secondary • Tertiary • Quaternary

• Unique sequence of amino acids • Important both genetically and structurally • Determined by order of mRNA • Protein organisation direct consequences of 1st structure (if primary structure is changed the whole protein changes) • The AA sequence of insulin was first determined in 1955 • Frederick Sanger won the Noble Prize in chemistry in 1958

Single amino acid substitution in haemoglobin - charged glutamic acid replaced by non-polar valine • Causes haemoglobin to crystallise • Distorted cell shape - limits oxygen supply to tissue • Sickle-cell disease (inherited condition) • Immune to malaria