7.1 Proteins
Proteins are polymers made of amino acids, joined by peptide bonds (-CONH- units) joining the main carboxyl group of one monomer with the alpha-amino group of the next monomer. Therefore, proteins are polyamides. The monomers are called residues, I'm not sure why. There are 20 proteinogenic amino acids, meaning they participate in protein formation. (A few species of microbes have an extra amino acid, making a total of 21.) The amino acids differ by their side chains, which are the functional groups that give each amino acid its own roles and properties in proteins. The atoms that are not part of the side chains form the protein's backbone. The 20 normal amino acids are:
L-methionine |
L-alanine |
L-isoleucine |
L-leucine |
L-valine |
L-aspartic acid |
L-glutamic acid |
L-lysine |
L-arginine |
L-cysteine |
L-asparagine |
L-glutamine |
L-serine |
L-threonine |
glycine |
L-histidine |
L-phenylalanine |
L-tryptophan |
L-tyrosine |
L-proline |
All proteinogenic acids have an alpha carbon, or Cα, bonded to an amino group and a carboxyl group. The heavy atoms of the side chain are designated beta, gamma, delta, and so on.
Two of the amino acids have acidic side chains, aspartic acid and glutamic acid. Two more amino acids have basic side chains, lysine and arginine. Someone once asked me how it can be basic if it's an acid, and I was at a loss as to how to answer. But the fact that it's an amino acid means it is already both an acid and a base, since amines are bases, and adding an extra acidic or basic side chain doesn't change that, but makes the whole molecule acidic or basic on average.
Two of the amino acids are amide equivalents of the acidic side chains: asparagine and glutamine. Their side chains are neither acidic nor basic, but are very polar and very hydrophilic. Two more are alcohols and are polar and moderately hydrophilic: serine and threonine.
The amides, alcohols, acids, and bases, being hydrophilic, most often occur on the outer surfaces of proteins.
Cysteine (rhymes with "sixteen") is a sulfur analog of serine. It is hydrophobic and has a special function: it creates disulfide bonds that cross-link protein strands together. Two cysteine molecules joined together by a disulfide bond is called a molecule of cystine (rhymes with "this time"). Many proteins rely on cystine cross links to keep their shape, and cystine cross links produce the toughness of the collagen in skin and the keratin in hair, nails, scales, claws, and feathers. Eggs taste like sulfur because the developing chick embryo needs sulfur to grow its feathers.
Cysteine is the only one of the normal 20 amino acids that occurs naturally as the (R)- isomer, rather than the (S)- isomer, however (R)-cysteine is nevertheless called L-cysteine by analogy since it has the amino and carboxyl groups in the same places as the other L-amino acids.
Five of the amino acids have aliphatic side chains: methionine, alanine, isoleucine, leucine, and valine (the MAILV group). Methionine's side chain is considered aliphatic because its sulfur atom is bonded only to carbon, with practically no difference in electronegativity, and is therefore for all intents and purposes totally nonpolar. The hydrophobic amino acids are often found in the inside parts of proteins.
Glycine has no side chain and is the only achiral amino acid. It is the most flexible of the amino acids.
Proline is the opposite of glycine in that it is the most rigid amino acid. While the other aminos can rotate about their N-Cα and Cα-C bonds, proline's nitrogen atom is part of its ring and can rotate very little. A proline residue causes a kink in the chain, and can disrupt the structure of the protein causing a change from one domain (structural piece) to another.
Four of the amino acids have aromatic side chains: histidine, phenylalanine, tyrosine, and tryptophan. They are hydrophobic and, like the aliphatic side chains, tend to occur inside protein structures.
Histidine is often considered a basic amino acid because of its ability to become protonated. However, protonation of histidine happens mostly in acidic conditions; its pKa (the pH at which half of the molecules are protonated) is only about 6.0. Positively charged histidine is indeed hydrophilic and basic, but neutral histidine is not, and behaves more like phenylalanine. But histidine has important functions in enzymes, where the ability of its imidazole ring to switch between its two tautomers allows histidine to move protons around.
More properties of the amino acids, including one that we'll come back to a little later:
| Letter | Code | Name | side chain pKa | α-helix penalty |
|---|---|---|---|---|
| A | Ala | L-alanine | - | 0.00 |
| R | Arg | L-arginine | 12.48 | 0.88 |
| N | Asn | L-asparagine | - | 2.72 |
| D | Asp | L-aspartic acid | 3.90 | 2.89 |
| C | Cys | L-cysteine | 8.37 | 2.85 |
| E | Glu | L-glutamic acid | 4.07 | 1.67 |
| Q | Gln | L-glutamine | - | 1.63 |
| G | Gly | glycine | - | 4.18 |
| H | His | L-histidine | 6.04 | 2.55 |
| I | Ile | L-isoleucine | - | 1.72 |
| L | Leu | L-leucine | - | 0.88 |
| K | Lys | L-lysine | 10.54 | 1.09 |
| M | Met | L-methionine | - | 1.00 |
| F | Phe | L-phenylalanine | - | 2.26 |
| P | Pro | L-proline | - | 13.22 |
| S | Ser | L-serine | - | 2.09 |
| T | Thr | L-threonine | - | 2.76 |
| W | Trp | L-tryptophan | - | 2.05 |
| Y | Tyr | L-tyrosine | 10.46 | 2.22 |
| V | Val | L-valine | - | 2.55 |