And yet it functions!

A nice paper adressing the issue of how mesophilic/thermophilic enzymes functions at differents temperatures is just out in Biochemistry [see here].

The work by the group of EA Eisenmesser focuses on the behavior of the cyclophilin enzyme from Geobacillus kaustophililus (GeoCyp), a bacterium found in the the deep see sediment of the Mariana Trench,  and compared to its mesophilic homologous from humans (CypA). The study demonstrates that, at variance with other mesophilic/thermophilic pair, here, the thermophile maintains up to 70% of its catalytic power at low temperature where most of thermophiles do not function or have very limited activity. We have already posted on the "corresponding state principle", introduced to explain why most of thermophiles lack activity at ambient conditions. According to this view, the lack of activity is due to the enhanced rigidity of the protein matrix which compromises mobility essential to the catalytic turn-over. At the same time mechanical rigidity is postulated as the source of the enhanced stability of the protein and its resistance to thermal stress. The universality of this principle has been questioned by showing that in many cases thermophiles can be as flexible as their mesophilic variants at the same thermodynamic conditions, thus stability is the results of a smaller entropy penalty between folded (less entropic) and unfolded (more entropic) states. 

According to the work by Eisenmesser and coworkers, the thermophilic GeoCyp is highly similar from the structural point of view to the human CypA, and its dynamics at different timescales is comparable even if its mobility seems more sensitive to temperature increases. What probably causes the 30% drop of activity at low temperature (10°C) with respect to activity at its optimal temperature (60°C) is a reduced local motion of binding-site loop, which gating is affected by the presence of a charged amino-acid, and a slightly less strong electric field measured at the level of the catalytic site and supposed to ease the isomerization of the peptide bond. In summary, this study shows us another deviation from the common believe based on the observation of reduced thermophilic activity at low temperatures. Nice work!