Glycine

Standard codons for G : GGA GGC GGG GGT

Substitution preferences:
All protein types:
Favoured
Neutral Ala ( 0) Asn ( 0) Ser ( 0)
Disfavoured Asp (-1) Glu (-2) His (-2) Lys (-2) Pro (-2) Gln (-2) Arg (-2) Thr (-2)
Trp (-2) Cys (-3) Met (-3) Phe (-3) Tyr (-3) Val (-3) Ile (-4) Leu (-4)

Intracellular proteins:
Favoured
Neutral Ala ( 0) Arg ( 0) Asp ( 0) Ser ( 0) Lys ( 0) Pro ( 0) Asn ( 0) Gln ( 0)
Disfavoured Cys (-1) Glu (-1) His (-1) Thr (-1) Val (-2) Trp (-2) Tyr (-2) Met (-2)
Leu (-3) Phe (-3) Ile (-3)

Extracellular proteins:
Favoured
Neutral Ala ( 0) Gln ( 0) Pro ( 0) Asp ( 0) Thr ( 0) Asn ( 0) His ( 0) Arg ( 0)
Ser ( 0)
Disfavoured Glu (-1) Lys (-1) Met (-2) Leu (-2) Val (-2) Trp (-2) Ile (-2) Tyr (-2)
Phe (-3) Cys (-6)

Membrane proteins:
Favoured Glu ( 3) Asp ( 3) Ser ( 1) Ala ( 1)
Neutral Arg ( 0) Thr ( 0)
Disfavoured Pro (-1) Gln (-1) Cys (-1) Val (-1) Lys (-1) Asn (-2) Ile (-2) Trp (-2)
His (-3) Met (-3) Leu (-4) Tyr (-5) Phe (-5)

Substitutions: As can be seen above, Glycine generally prefers to substitute with other small amino acids. However it structure can mean that even apparently neutral mutations (e.g. to Alanine) can be forbidden in certain contexts (see below).

Role in structure: Glycine is a very unique amino acid in that in contains a hydrogen as its side chain (rather than a carbon as is the case in all other amino acids). This means that there is much more conformational flexibility in glycine. What this means is that glycine can reside in parts of protein structures that are forbidden to all other amino acids (e.g. tight turns in structures). Role in function: The uniqueness of Glycine also means that it can play a distinct functional role, such as using its sidechain-less backbone to bind to phosphates. This means that if one sees a conserved glycine changing to any other amino acid (i.e. even those listed above), the change could have an impact.

A good example is found in protein kinases:

The above shows a region around the ATP binding site in a protein kinase. The ATP is shown to the right of the figure, and part of the protein to the left. The Glycines in this loop are colour red, and are part of the classic "Gly-X-Gly-X-X-Gly" motif present in the kinases. These three Glycines are almost never mutated to other residues; this is particularly true of the second Glycine (labelled GLY13.CA in the figure), which must be Glycine in order to bind to the phosphates (orange and red atoms) of the ATP molecule.

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Please cite: M.J. Betts, R.B. Russell. Amino acid properties and consequences of subsitutions.
In Bioinformatics for Geneticists, M.R. Barnes, I.C. Gray eds, Wiley, 2003..