Protein methylation is an important biological process e.g.
histone lysine methylation is involved in both gene activation (on histone 3 and Lys 4, 36 and 79) and silencing (H3 Lys 9 or 27 and H4 Lys 20). But how can
other protein methyltransferases (PMTs) be investigated? Genetic approaches are
always useful, but can have limitations particularly if your protein isn’t very
common, forms complexes with other proteins (which would be disrupted by its
absence and cause phenotypic changes beyond protein methylation) or if your
process results in a non-viable cell. Chemical approaches would be extremely
useful and complimentary, but as always problems with selectivity have to be
overcome; a particular problem with PMTs as SAM (S-Adenosyl methionine) is a
particularly prolific enzyme co-factor.
What to do then? Islam et. al. have developed a rather elegant
solution that could allow general examination of a variety of PMTs, by creating
mutants of proteins that can accept a synthetic azido-SAM donor. The enzyme
then tags its target as before but instead of a methyl an azide containing group is left
behind, this can subsequently be reacted with tags (like biotin) which
contain strained alkynes in a bio-orthogonal manner.
