#35 Interconversion of Encoded Amino Acids

[John S. Garavelli]

On 06/01/2010 14:51, "D'Eustachio, Peter" <Peter.D'Eustachio at nyumc.org> sent this request:
We're in the final stages of converting the way we handle modified-residue instances in Reactome to be compliant with MOD usage, and need seven new MOD terms. (We also need to continue the discussion from December about how to annotate an incompletely specified modification - dextrin attached to 4'O of tyrosine, for example, but we have a workaround for that right now so it's not urgent.)

The new terms would all be analogous to MOD:00537 "A protein modification that effectively converts an L-threonine residue to L-alanine."

We need:
- conversion of L-lysine to L-proline
- conversion of L-proline to L-aspartate
- conversion of L-proline to L-lysine
- conversion of L-asparagine to glycine
- conversion of L-threonine to L-threonyl-arginyl-arginine (the single amino acid is replaced by three, effectively a two-residue insertion in the polypeptide)
- conversion of L-asparagine to L-lysine
- conversion of L-lysine to L-glutamate

(All are found in genetically engineered forms of human insulin, where they affect the half-life and activity of the protein after injection into the patient.)

On 15/01/2010 15:35, "D'Eustachio, Peter" <Peter.D'Eustachio at nyumc.org> sent this request:
In addition to the items listed below, could we have two more:

- conversion of L-isoleucine to L-valine
- conversion of L-glutamine to L-arginine

[John S. Garavelli]

Since these "conversions" are produced by genetic manipulation, and not by direct chemical modification as the mass-spectrometrists would be expecting, and more than 400 distinct terms would have to be created, instead this was implemented by introducing terms for replacement by or insertion of each of the natural, encoded amino acids (the children of MOD:01441 natural, standard, encoded residue) and for the replacement or removal of each of the natural, encoded amino acids (the children of MOD:01651 natural, standard, encoded residue removal) with negative difference formulas and masses. By combining two or more of these forty terms, any engineered or natural mutation can be represented. The combining of modification terms had been anticipated for modifications combining both amino acid terminal groups and side chains, and in some cases for different locations of the side chains. It is important that the implementations of PSI-MOD take into account this possible combination of terms.
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