Protein

Myoglobin- The first protein whose structure was determined by x-ray crystallography

1. All proteins are made up of amino acids
2. There are twenty standard amino acids, each of which include a carboxyl group, a amino group, a hydrogen, and a side group all bonded to a chiral carbon center.
3. All amino acids residues are L-stereoisomers. Rememeber the convention from glyceraldehyde.
4. All amino acids other than glycine have a chiral carbon.
5. Free amino acids are zwitterion at neutral pH. The amino group is protonated the carboxylic group is deprotonated.

The 20 Amino acids

• non-polar, aliphatic – alanine (Ala, A), valine, (Val, V), leucine (Leu, L), isoleucine (Ile, I), also glycine (Gly, G), proline (Pro, P)
• aromatic – phenylalanine (Phe, F), tyrosine (Tyr, Y), Tryptophan (Trp, W)
• polar, uncharged – serine (Ser, S), threonine (Thr, T), asparagine (Asn, N), glutamine (Gln, Q)
• positively charged – arginine (Arg, R), lysine (Lys, K), histidine (His, H)
• negatively charged – aspartate (Asp, D), glutamate (Glu, E)
• sulfur-containing – methionine (Met, M), cysteine, (Cys, C),
• Other ‘non-standard’ amino acids are found in some proteins

Peptide bonds (linking amino acids together)

• The amino acids are joined by peptide bonds from dehydration from the alpha-carboxyl group of one amino acid and the alpha-amino group of another. There is a partial double bond character of the peptide bond which prevents rotation, therefore the bond is planar.
• The peptide bond can exist in two conformations (cis and trans). Peptide bonds are generally in the trans formation. This key fact influences the types of secondary structure than form.
• The sequences of peptides are always written from the N-terminal end to the C-terminal end

Primary Sequence

The amino acids within a protein can be described in two ways:

• Amino acid composition, what amino acids are present
• Amino acid sequence, the order of the amino acids

Secondary Structure

• The secondary structure describes the relative orientations of amino acids close in sequence. There are two predominant structure alpha helix and beta sheets.
• Secondary strucutre is mainly influenced by primary structure although this is not generally true.
• Some residues are better in a certain type of secondary structure than another.
• Tertiary structure can sometimes influence secondary structure.
• Helix is stabilized by hydrogen bonding between the hydrogen attached to the nitrogen of each peptide bond and the carbonyl oxygen of the fourth amino acid to the N-terminus. Every residue participates in this interaction except those near the ends of the helix. Only certain amino acids are structurally capable of forming helices.
• Beta Sheets are stabalized a different way. Instead of hydrogen bonds between amino acids close in primary sequence, the beta confimration is stabilized by H-bonds between groups of residues that exist in the beta confirmation.

Tertiary structure: the arrangement of secondary structure to form an overall three-dimensional structure.

Tertiary structure typically seen:

• Most hydrophobic side chains are buried away from water
• Typicaly compact
• Most charged chains are on the outer face hydrated to water molecules
• The native tertiary structure is only seen udner a particular physiological condition.
• Tertiary structures are stabalized by hydrogen bonding, electrostatic ineractions, covalent bonding, hydrophobic forces
• The biggest contributing factor to tertiary structure comes fromt he hydrophobic forces

Quaternary structure- Oligomeric proteins (those with more than one separate polypeptide chain) can be very complex.

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Hemoglobin- A heteromeric protein which contains 2 a and 2 b subunits. Quarternary structure holds the heteromeric protein together.

Protein Folding

• Folding is spontaneous; the final structure is determined by the primary sequence
• Folding generally occurs in a step by step or hierachial manner; local secondary stuctures come together to form tertiary structure etc
• Many proteins require helper proteins called chaperones ot help fold into the proper native structure.