Non-proteinogenic amino acids

Some non-α-amino acids exist in organisms. In these structures, the amine group displaced further from the carboxylic acid end of the amino acid molecule. Thus a β-amino acid has the amine group bonded to the second carbon away, and a γ-amino acid has it on the third. Examples include β-alanine, GABA, and δ-aminolevulinic acid.

• 
  β-alanine: an amino acid produced by aspartate 1-decarboxylase and a precursor to coenzyme A[7] and the peptides carnosine and anserine.
• 
  γ-Aminobutyric acid (GABA): a neurotransmitter in animals.
• 
  δ-Aminolevulinic acid: an intermediate in tetrapyrrole biosynthesis (haem, chlorophyll, cobalamin etc.).
• 
  4-Aminobenzoic acid (PABA): an intermediate in folate biosynthesis

The reason why α-amino acids are used in proteins has been linked to their frequency in meteorites and prebiotic experiments.[8] An initial speculation on the deleterious properties of β-amino acids in terms of secondary structure[8] turned out to be incorrect.[9]

Some amino acids contain the opposite absolute chirality, chemicals that are not available from normal ribosomal translation and transcription machinery. Most bacterial cells walls are formed by peptidoglycan, a polymer composed of amino sugars crosslinked with short oligopeptides bridged between each other. The oligopeptide is non-ribosomally synthesised and contains several peculiarities including D-amino acids, generally D-alanine and D-glutamate. A further peculiarity is that the former is racemised by a PLP-binding enzymes (encoded by alr or the homologue dadX), whereas the latter is racemised by a cofactor independent enzyme (murI). Some variants are present, in Thermotoga spp. D-Lysine is present and in certain vancomycin-resistant bacteria D-serine is present (vanT gene).[10][11]

All proteinogenic amino acids have at least one hydrogen on the α-carbon. Glycine has two hydrogens, and all others have one hydrogen and one side-chain. Replacement of the remaining hydrogen with a larger substituent, such as a methyl group, distorts the protein backbone.[8]

In some fungi α-aminoisobutyric acid is produced as a precursor to peptides, some of which exhibit antibiotic properties.[12] This compound is similar to alanine, but possesses an additional methyl group on the α-carbon instead of a hydrogen. It is therefore achiral. Another compound similar to alanine without an α-hydrogen is dehydroalanine, which possess a methylene sidechain. It is one of several naturally occurring dehydroamino acids.

• 
  alanine
• 
  aminoisobutyric acid
• 
  dehydroalanine

A subset of L-α-amino acids are ambiguous as to which of two ends is the α-carbon. In proteins a cysteine residue can form a disulfide bond with another cysteine residue, thus crosslinking the protein. Two crosslinked cysteines form a cystine molecule. Cysteine and methionine are generally produced by direct sulfurylation, but in some species they can be produced by transsulfuration, where the activated homoserine or serine is fused to a cysteine or homocysteine forming cystathionine. A similar compound is lanthionine, which can be seen as two alanine molecules joined via a thioether bond and is found in various organisms. Similarly, djenkolic acid, a plant toxin from jengkol beans, is composed of two cysteines connected by a methylene group. Diaminopimelic acid is both used as a bridge in peptidoglycan and is used a precursor to lysine (via its decarboxylation).

• 
  cystine
• 
  cystathionine
• 
  lanthionine
• 
  djenkolic acid
• 
  diaminopimelic acid

The genetic code has been described as a frozen accident and the reasons why there is only one standard amino acid with a straight chain (alanine) could simply be redundancy with valine, leucine and isoleucine.[8] However, straight chained amino acids are reported to form much more stable alpha helices.[13]

• 
  glycine (hydrogen side-chain)
• 
  alanine (methyl side-chain)
• 
  homoalanine, or α-aminobutyric acid (ethyl side-chain)
• 
  norvaline (n-propyl side-chain)
• 
  norleucine (n-butyl side-chain)
• 
  homonorleucine (n-Pentyl side-chain, heptanoic acid shown)

Serine, homoserine, O-methylhomoserine and O-ethylhomoserine possess a hydroxymethyl, hydroxyethyl, O-methylhydroxymethyl and O-methylhydroxyethyl side chain; whereas cysteine, homocysteine, methionine and ethionine possess the thiol equivalents. The selenol equivalents are selenocysteine, selenohomocysteine, selenomethionine and selenoethionine. Amino acids with the next chalcogen down are also found in nature: several species such as Aspergillus fumigatus, Aspergillus terreus, and Penicillium chrysogenum in the absence of sulfur are able to produce and incorporate into protein tellurocysteine and telluromethionine.[14]

Despite not being encoded by the genetic code as proteinogenic amino acids, some non-standard amino acids are nevertheless found in proteins. These are formed by post-translational modification of the side chains of standard amino acids present in the target protein. These modifications are often essential for the function or regulation of a protein; for example, in γ-carboxyglutamate the carboxylation of glutamate allows for better binding of calcium cations,[16] and in hydroxyproline the hydroxylation of proline is critical for maintaining connective tissues.[17] Another example is the formation of hypusine in the translation initiation factor EIF5A, through modification of a lysine residue.[18] Such modifications can also determine the localization of the protein, for example, the addition of long hydrophobic groups can cause a protein to bind to a phospholipid membrane.[19]

• 
  Carboxyglutamic acid. Whereas glutamic acid possess one γ-carboxyl group, Carboxyglutamic acid possess two.
• 
  Hydroxyproline. This imino acid differs from proline due to a hydroxyl group on carbon 4.
• 
  Hypusine. This amino acid is obtained by adding to the ε-amino group of a lysine a 4-aminobutyl moiety (obtained from spermidine)
• 
  Pyroglutamic acid

There is some preliminary evidence that aminomalonic acid may be present, possibly by misincorporation, in protein.[20][21]