Today’s #365papers is about the topics of protein dynamics, their role in enzymes and some insights into their role in evolution.
Maintenance of Native-like Protein Dynamics May Not Be Required for Engineering Functional Proteins Sophie M.C. Gobeil et al. Chemistry & Biology, 21 (10), pp. 1330-1340 http://dx.doi.org/10.1016/j.chembiol.2014.07.016
The authors study and characterise extant β-lactamases and generate a chimera between two enzymes with similar dynamic behaviour. Although the kinetic properties of the chimera are in line with its parents’, major changes in structural dynamics can be observed by NMR. These changes seem to affect the active site conformation, but affect catalytic efficiency only to a minor extent.
I believe that more evidence on other enzymes/chimeras is needed before any generalisation can be driven. For the time being, this study suggests how dynamics could be less constrained during functional evolution than current scenarios suggests. Hence, not only dynamics could allow functional innovation (by providing access to alternative conformers), but they might themselves evolve.
Years ago I was studying thermal adaptation in enzymes, and came across the (at the time) unexpected result of an increase in thermal stability being accompanied by a relocation (as opposed to a decrease) in structural flexibility at sites distant from mutations (shameless plug paper here).
Although our study was less detailed than the one I’m presenting today, and structural analysis based on molecular dynamics, that changes in dynamics could play a pivotal role in enzyme and protein evolution has been brewing in the back of my mind ever since.