Cold Adaptation of Triosephosphate Isomerase

Area of Science:

• Biochemistry
• Structural Biology
• Enzymology

Background:

• Psychrophilic enzymes must function near water's freezing point, facing reduced reaction rates.
• Cold adaptation involves shifting the activation enthalpy-entropy balance compared to mesophilic counterparts.

Purpose of the Study:

• To investigate the structural basis for altered activation free energy in cold-adapted enzymes.
• To compare the temperature dependence of activation free energy in psychrophilic and mesophilic triosephosphate isomerases.

Main Methods:

• Molecular dynamics free energy calculations.
• Empirical valence bond method.
• Analysis of orthologous enzymes with known 3D structures.

Main Results:

• The psychrophilic Vibrio marinus triosephosphate isomerase exhibits the characteristic enthalpy-entropy balance shift compared to the yeast ortholog.
• Differential mobilities in surface-exposed protein loops were identified as the origin of this shift.
• Key mutations in these loops increase mobility, reducing activation enthalpy and thermostability.

Conclusions:

• Surface loop dynamics are crucial for the cold adaptation of triosephosphate isomerase.
• Increased loop mobility in psychrophilic enzymes contributes to their functional efficiency at low temperatures.
• This adaptation comes at the cost of reduced overall thermostability.