Lecture 1: Introduction to protein structure 1) Describe the three main groups into which amino acids may be placed on the basis of the chemical nature of their side chains. • Amino acids with non-polar (hydrophobic) side chains • amino acids with polar (hydrophilic) side chains; • amino acids with charged (hydrophilic) side chains. 2) Outline the reaction in which amino acids are joined together. • Peptides are formed by a condensation reaction. The –OH group of a carboxyl group of one amino acid and a hydrogen from the amino group of another amino acid are released in the form of H2O resulting in a peptide bond between the two adjacent amino acids. 3) Sketch a trimeric peptide, illustrating the amino terminus, carboxyl terminus and side chains.
4) Give examples of the post translation modifications of amino acids. • Post-translation enhances the capabilities of the protein. • The addition of hydroxyl groups (eg. proline to hydroxyproline in collagen fibres- the constituent of skin, cartilage, teeth, bone etc…), the addition of the hydroxyl group helps to stabilise the fibres (hence a defiency in vit. C- which catalyses the hydroxyl reaction leads to scurvy) • N-linked glycosylation of asparagine residues of proteins increases their solubility and protects against enzymatic degradation; • carboxylation of glutamate (addition of a –COO- group), to give y-carboxyglutamate, which is critical for proteins within the blood clotting cascade as it increases their calcium binding ability. 5) Define the terms primary structure, secondary structure, tertiary structure & quaternary structure with respect to proteins. • Primary structure – Simply the linear sequence of amino acids that make up the protein. • Secondary structure – Local structural motifs within a protein eg. α–helices and β–pleated sheets; their existence within a protein is dictated by the primary structure or amino acid sequence. • Tertiary structure - the arrangement of the secondary structure motifs into compact globular structures called domains. • Quaternary structure - Defined as the three dimensional structure of a multimeric protein composed of several subunits. (i.e the interaction of several proteins) 6) Distinguish between an α helix and a β pleated sheet. • The main chain of a protein is highly polar and therefore hydrophilic (due to the C=O and NH groups. Therefore it seems as though the protein could not fold into an interior protein. However neutralisation of the polar groups is achieved by their H-bonding to form 1 of 2 regular structures: α–helix, β-pleated sheet. • The side chains of individual amino acids project out from within the α–helix. H-bonds between the C=O of one residue and the NH of another residue 4 amino acids along the helix, stabilise the entire structure. There is a occasionally a slight kink in the helical structure, this is due to the presence of proline as one of the amino acids. In proline the last atom of the chain is bonded to the main chain N atom, this prevents the N atom from hydrogen bonding with the C=O groups of another residue in the helix, thereby distorting the helical conformation, putting a kink into it. • In the β-pleated sheet, the NH and C=O groups point out at right angles to the line of the backbone. This almost two dimensional sheet is pleated, like the bellows of an accordion. As with the alpha helix, hydrogen bonds between the NH and C=O groups of two or more b-strands hold the β-pleated sheet together. β-strands can run in the same direction to give a parallel β-pleated sheet, or in opposite directions to give an antiparallel β-pleated sheet. 7) Give examples of the types of bond involved in holding proteins together. • Covalent bonds are the strongest bonds in the protein existing in the primary structure itself. Covalent bonds can also exist as disulphide bridges. These occur when cysteine side chains within a protein are oxidised resulting in a covalent link between the two amino acids. • Hydrogen bonds occur when 2 atoms bearing negative charges, partially share a positively charged hydrogen. These can occur between atoms on different side chains and the back bone of the protein or between H20 molecules.
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