I don’t agree that I’m doing that because I specifically made sure to point out it was the combination of structure and function that Axe purports to measure, at least according to Ann Gauger.
But more importantly, on nomenclature: According to SCOP that is literally the name for the fold. The structure is named by the functions known to be carried out by it.
Fold e.3: beta-lactamase/transpeptidase-like
And yes, they are not actually measuring this relationship. Truth is Axe has no idea what structure his mutant enzymes have adopted after mutagenesis. He never does anything like crystal structures or what have you. He just looks to see if colonies form on agar plates. Kinda strange for a piece of work advertised to probe the relationship between structure, function, and sequence space.
Yes and that’s the real thing that matters in evolution, function or degree of function.
He argues (completely unsuccessfully) in his 2004 paper that this is what he is trying to do, find a sort of base of the hill of activity that provides a fitness benefit because in his mind an enzyme like this would have to sort of evolve de novo (the actual main conceptual flaw of their argument), and this would be much more likely to find some weakly active variant than the global peak (true, but irrelevant).
You could argue that if he really wants to establish some estimate of how weakly functional an enzyme can get and still provide a fitness-benefit to the organism, and with this information try to estimate how many sequences could meet or exceed that threshold for functionality, his protocol would at some point have to include actual tests to see where the activity of his mutant enzymes provide enough of a fitness-benefit to incur a growth advantage under very low concentrations of antibiotic.
But that would also have to be well below the minimum inhibitory concentration (MIC). That is after all where bacteria are thought to develop resistance in the first place, where the concentration of antibiotic is low enough to not entirely arrest growth and kill them, but merely slow it down enough that mutations can result in beneficial effects large enough to be visible to selection.
It is interesting to consider in how many ways his paper fails to be what it claims to be, and what one should have done instead to at least try to estimate what they claim he estimated.