Amino Acids and protein structure.docx
Transcript
Structure of amino acids Has a central carbon, amino group, carboxyl group, a hydrogen and a R group. All but one of the amino acids out of 20 has a chiral carbon. Meaning it has 4 different chemical groups attached therefore can have L or D isomers. Only L amino acids are in proteins. Only glycin...
Structure of amino acids Has a central carbon, amino group, carboxyl group, a hydrogen and a R group. All but one of the amino acids out of 20 has a chiral carbon. Meaning it has 4 different chemical groups attached therefore can have L or D isomers. Only L amino acids are in proteins. Only glycine does not have a chiral carbon because there are only 3 different groups attached instead of 4 different groups being attached. The R group in glycine is a hydrogen. Different amino acids can vary in size, shape, charge polarity and chemical reactivity. Need to know the key features of amino acids such as if names were given should know if its size, polarity and whether it has something unique about it. Amino acids in solution tend to exist as zwitterions (both COOH and NH2 gets ionised)- the nature of species present depends on the PH. Low ph= both COOH and NH3 gets protonates and a net charge of +1 High ph= both COOH and NH3 gets deprotonated which gives NH2 and COO- and net charge of -1 pKa= the pH at which the concentrations of the protonated and unprotonated forms are equal Ionisation state varies with pH pKa for COOH is around 2. At pH below 2, its COOH At pH higher than 2, it gets ionised into COO- and H+ pKa for amino group is between 9-10 at pH below 9, its NH3+ (protonated charged form) at pH above 10, its deprotonated into NH2 and H+ 7 of the 20 amino acids have readily ionisable side chains. In contrast Primary and secondary structure Peptide bond gets formed between the carboxyl group of one amino acid and the amino group of the other amino acid- covalent bond and releases water. Each of the other amino acid that gets joined to the chain is referred to as a residue. Every polypeptide has a free amino group at one end and a free carboxyl group at the other end. Always refer to proteins in direction of amino to carboxyl. The primary structure is the amino acid sequence in the polypeptide chain. Every primary structure is different. Function depends upon amino acid sequence. Proteins fold up into different 3D structures essential for the function is determined by the amino acid sequence. Chain of amino acids can fold up to form either alpha helix or beta sheets- secondary structure. Secondary structure Sequence of amino acid linked by hydrogen bonds (occurs between the N-H and C=O) to form repeating structures such as: Alpha- helices Beta- sheets Turns and loops. Alpha-helices One amino acid that’s not found in alpha-helices is proline due to the side chain that bends back onto amino group which prevents it from forming hydrogen bond. Alpha helix is a right-handed helix- you go from left to right as you go up the helix. Has 36 amino acids per 10 turns= 3 amino acids per turn. The C=O group of a residue hydrogen bonds with N-H group of a residue 4 along the sequence. Beta-sheets 2 or more polypeptide strand line up and hydrogen bonding occurs to hold them as sheets. Strands can be parallel or anti-parallel. Can also have beta-sheets with mixture of parallel and anti-parallel strands. The side chains of the amino acids stick out above and below the beta-sheet. Turns and loops. Residues proline and glycine are commonly found. Tertiary and quaternary structure Tertiary structure Proteins overall 3D structure of all atoms in a polypeptide chain. Alpha-helices and beta-pleated sheets fold together to form a compact structure. Stabilised by multiple weak bonds. Proteins fold into lowest energy conformation. The main factor in driving folded structure is the hydrophobic effect. Most proteins are in aqueous environment aqueous environment. Hydrophobic chains bury in the core away from the water. Any amino acid side chains which are charged or polar interact with the aqueous environment. The structure is held together via multiple non-covalent bonds. Electrostatic forces between charged side chains. Hydrogen bonds between polar groups London forces Prosthetic groups Some proteins include additional non-protein element such as prosthetic group Co-factors Co enzymes These are tightly bound in the 3D structure, can be critical for function. Eg= haem groups, metal ions and lipids Quaternary structure Multiple polypeptide chains join to form multi-subunit structures. Stabilised by the same type of multiple weak forces of interaction as tertiary. Simplest form= dimer Can be homo or heterodimers. Oligomers often form symmetrical or repeating structures such as haemoglobin. Cystine is a unique amino acid as it’s the only one with SH group that can form disulphide bonds- covalent cross-links so they are very strong compared to other bonds. Can be either: Intrachain= between 2 cystines in the same polypeptide chains Interchain= between cysteines in different polypeptide chains. Domain= part of polypeptide chain that folds independently into a compact structure. Protein denaturation Extreme pH, detergents, temperatures etc can denature the protein as the proteins folded structure is held together via weak forces. Results in loss of function as function is dependent on the shape. Disulphide bonds can be broken by reducing agents. Primary structure aka peptide bonds are never broken or effected as they are strong. Renaturation isn’t always possible but is possible. Cystic fibrosis ////// Sickle cell anaemia /////
