Adaptations for Pressure and Temperature in Dihydrofolate Reductases

Enzymes from extremophilic microbes that live in extreme conditions are generally adapted so that they function under those conditions, although adaptations for extreme temperatures and pressures can be difficult to unravel. Previous studies have shown mutation of Asp27 in Escherichia coli dihydrofolate reductase (DHFR) to Glu27 in Moritella profunda (Mp). DHFR enhances activity at higher pressures, although this may be an adaptation for cold. Interestingly, MpDHFR unfolds at similar to 70 MPa, while Moritella yayanosii (My) was isolated at depths corresponding to similar to 110 MPa, indicating that MyDHFR might be adapted for higher pressures. Here, these adaptations are examined using molecular dynamics simulations of DHFR from different microbes in the context of not only experimental studies of activity and stability of the protein but also the evolutionary history of the microbe. Results suggest Tyr103 of MyDHFR may be an adaptation for high pressure since Cys103 in helix F of MpDHFR forms an intra-helix hydrogen bond with Ile99 while Tyr103 in helix F of MyDHFR forms a hydrogen bond with Leu78 in helix E. This suggests the hydrogen bond between helices F and E in MyDHFR might prevent distortion at higher pressures.

Automated summary

Enzymes from extremophilic microbes are generally adapted to function in extreme conditions, but adaptations for high temperatures and pressures can be challenging to understand. Studies suggest that some microbial enzymes may have specific adaptations for high pressure, such as Tyr103 in MyDHFR possibly playing a role in adaptation to high pressures.