Beta-Lactamase, Antibody Enzymes, and Sequence Space

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This is a distinction without significance for three reasons:

  1. A stable fold is not a requirement for an enzyme in the first place. Intrinsically disordered proteins are likely an important initial state for de novo enzymes, that are subsequently tightened up into a stable fold by positive selection. For an IDP to work as an enzyme, it needs one groove in the protein to be in the right configuration some of the time. That isn’t too hard to do, and might even be easier for an IDP than a stable protein.

  2. It is fairly easy to get a stable fold. Right now, protein prediction algorithms are good enough to study this. Put some random sequences in. See how often stable folds arise. It is quite easy. (I think @T_aquaticus has done this before).

  3. An antibody is essentially a stable fold with a variable groove or pocket. Imagine a protein has one function, and is maintained by negative selection to be a stable fold. An “unused” groove of the protein can be varied by neutral evolution till it finds the function. Antibody evolution mimics this process. Add in the Real Time-Evolution mechanism you just wrote about (duplication-then-divergence), and you have a new enzyme, with a totally new function.

So for those three reasons, I do not think there is reason to doubt the relevance of these studies.

[EDIT: Removed discussion on CCC. It’s too late to get this straight.]

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