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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) |
| 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) |
| 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) |
| 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) |
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.