I’ve been thinking back to my bio-tinkering days. I used to work on protease inhibitors called serpins, serine protease inhibitors. Serine proteases are enzymes that cut up other proteins and have a serine (an amino acid) as the key component of the calalytic chemistry. The two main serpins I studied were practically identical except for the region that acted as bait for the serine protease in the inhibition process. And it turned out, one of the serpins actually inhibited cystein proteases, proteases of a different class, but which use a cystein as the key amino acid in a catalytic process almost identical to serine proteases (see figure to right).
Biochemists will find that cool, in a geeky way.
Site-directed mutagenesis
Furthermore, I showed that changing a few amino acids was enough to change a serine protease inhibitor into a cystein protease inhibitor, and vice versa. I did this by mutagenizing (a fancy word for changing) one amino acid of the protein at a time.
It was a fun process and what really appealed to me was being able to change the function of a protein at the atomic level.
As a grad student, I did similar work with DNA, effectively changing a few atoms to change the function of the DNA with respect to an enzyme that recognized it.
Taking that thought farther, yes, one could change all sorts of DNA and proteins molecules and create new functions. But that’s hard. Small changes, when you’re lucky, are not so hard. But, really crafting whole new types of enzymes or protein functions is the real alchemy of the 21st century as synthetic biology takes off.
Nature trumps all
Fun, though it is to create new functions for molecules, I do think nature has probably experimented with every chemistry possible and created a whole slew of useful enzymes. Will it be necessary to make new types of enzymes? I’m not sure. Nature is interested in a sub-set of chemistries that might be useful for us. We might be able to find an enzyme that suits our needs most of the time, but I think at some point we might need to modify, or even create, an enzyme with a new function.
And it’s already happening on the DNA level (making sequences better at binding proteins or promoting activity). But I haven’t really heard about folks messing with the proteins themselves.
