To kick off my 2015 resolution, here’s a paper that uses molecular modelling to correlate the observed promiscuity profile of o-Succinylbenzoate Synthase with the involvement of alternative amino acids within the same active site.
Enzyme Promiscuity in Enolase Superfamily. A Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM Methods M. Sánchez-Tarín, K. Świderek, M. Roca, and I. Tuñón http://pubs.acs.org/doi/abs/10.1021/jp511147b The Journal of Physical Chemistry B Just Accepted Manuscript
The authors find correlation between their findings (energy profiles of the two reactions) and experimental values and map the stabilising/destabilising effects of residues in the enzyme active site/binding pocket. Rearrangements in an active site conformation have been shown already to be favourable for promiscuity, and the current report suggest a similar scenario.
That enzyme and binding promiscuity enhances/allows the evolution of new functions is now an established concept, but the understanding of the molecular and structural features that can bring it about is still largely under-reported. Experimental and computational (as this one) analysis are thus very welcome.