alt Hacker NewsNone of this seems particularly surprising to someone who was an undergraduate level of biochemistry knowledge. Thirty years ago the professor in my Proteins class made a few relevant important points in his lectures:
1) Only handful of amino acids in a enzyme structures were highly conserved. (Out of hundreds, generally less than ten.)
2) Those were generally in the reaction center.
3) Almost all single sequence replacements had no measurable effect on protein structure and function.
4) Across species the "same" protein can diverge in sequence by up to 40%, while keeping the same structure. Sometimes this goes as far as 80%.
Given these basic facts, the findings in the paper aren't really surprising to anyone who studies proteins.
[Note: As with everything in biology, you can find counter examples. The histone proteins involved in DNA packing have an incredibly conserved sequence.]
Replies
You are missing the point - sure a particular enzyme's function is resilent to large levels of substitution because:
1. The number of residues actively involved in catalysis might be small and 2. Most other residues can be safely replaced with something else either similar if part of the structure or anything if the side chain is pointing out on the surface.
However, the point the article is making is that for different functions the same basic folds seem to be used again and again.
Is that because the stable protein fold structural space is actually small ( due to the limited secondard structure patterns used etc ), or is that because evolution hasn't had time to to search the enormous available structural space?
ie is it a sampling problem or an instrinic property of protein space.
The fact that some of the ML approaches mentioned can now design completely novel folds suggests it is at least partially a sampling problem.
This to me isn't surprising - the idea that evolution is somehow complete and all possible solutions have already been explored seems to me to be unlikely - a lot of evolution happens via gene duplication and then gradual functional drift - which would favour reuse of existing folds over the generation of completely new ones.
So what are the lessons here?
- that structure is as/more important than sequence ?
- that "reaction centers" are what matter, and the rest is just "protection" ?
What do you mean by "reaction center" - surely not physically central within the folded structure (isn't it the surface shape that determines reactivity) ?