Isoleucine



Standard codons for I : ATA ATC ATT

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

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

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

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


Substitutions: As Isoleucine is an aliphatic, hydrophobic, amino acid, it prefers substitution with other amino acids of the same type (see above).

Role in structure: Being hydrophobic, Isoleucine prefers to be buried in protein hydrophobic cores. However, Isoleucine has an additional property that is frequently overlooked. Like Valine, and Threonine it is C-beta branched. Whereas most amino acids contain only one non-hydrogen substituent attached to their C-beta carbon, these three amino acids contain two. This means that there is a lot more bulkiness near to the protein backbone, and thus means that these amino acids are more restricted in the conformations the main-chain can adopt. Perhaps the most pronounced effect of this is that it is more difficult for these amino acids to adopt an alpha-helical conformation, though it is easy and even preferred for them to lie within beta-sheets.

Role in function: The Isoleucine side chain is very non-reactive, and is thus rarely directly involved in protein function, though it can play a role in substrate recognition. In particular, hydrophobic amino acids can be involved in binding/recognition of hydrophobic ligands such as lipids.


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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.
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