I presented journal club today on the paper:
Pandya, C., Brown, S., Pieper, U., Šali, A., Dunaway-Mariano, D., Babbitt, P. C., et al. (2013). Consequences of domain insertion on sequence-structure divergence in a superfold. PNAS, 110(36), E3381–7. PMID:23959887
They look at structural diversity in the HAD superfamily, which consists of a Rossmann fold plus 0-2 large domain insertions. This leads to some interesting conclusions about how the inserted domain changes the structure of the core domain. For instance, the interface between the two domains is relatively similar regardless of what cap domain is inserted, yet more distant portions show definite patterns.
It is often difficult to make strong conclusions about fold space due to the large divergence within folds, which obscures the evolutionary signal. Pandya et. al strike a nice balance between well-supported claims about this single superfamily, and more speculative general hypotheses about evolution and protein fold space.
My slides are available on SlideShare.