Evolution cheats, or how to get an old enzyme to do new tricks

It is of course a cliche to state that eukaryotic cells (i.e., cells that are not bacteria) are complex. In the case of an animal, tens of thousands of proteins engage in fantastically elaborate interactions that somehow coax a single cell into generating a unique and magnificent organism. These interactions are often protrayed as exquisitely precise, using metaphorical images such as ‘lock-and-key’ and employing diagrams that resemble subway maps.

Many of these interacting proteins are enzymes that modify other proteins, and many of those enzymes are of a particular type called kinases. Kinases do just one thing: they attach phosphate groups to other molecules. This kind of modification is centrally important in cell biology, and one way to tell is to look at how many kinases there are: the human genome contains about 500 kinase genes.

Now, kinases tend to be pretty picky about who they stick phosphate onto, and this specificity is known to involve the business end of the kinase, called the active site. The active site is (generally) the part of the kinase that physically interacts with the target and transfers the phosphate. You might think that this interaction, between kinase and target, through the active site, would be by far the most important factor in determining the specificity of kinase function. But that’s probably not the case.