ABSTRACT

Enzyme Activity in Addition to Thermal Stability ............................ 56 3.4 Other Approaches Based on Rigidity Theory ................................................ 58 3.5 Conclusion ......................................................................................................60 Acknowledgments ....................................................................................................60 References ................................................................................................................60

proteins.1 In particular, the role of noncovalent interactions for the stabilization of a protein’s native tertiary structure has become the focus of protein science.2,3 Naturally occurring proteins from thermophilic organisms, referred to here as “thermophilic proteins,” retain their native structures up to temperatures of 80°C while their homologue counterparts from mesophilic organisms, referred to here as “mesophilic proteins,” denature.4-8 Thermophilic proteins are valuable for investigating the molecular forces that determine thermostability. Such knowledge can be applied to improve the thermostability of proteins from mesophilic organisms, which is an important task in engineering proteins for biotechnological and chemical applications.9 Comparative studies using homologues from mesophilic and thermophilic organisms have revealed that thermophilic adaptation often comes with better packing of hydrophobic interactions and an increased density of salt bridges or charge-assisted hydrogen bonds.10-12 In many cases, a complex interplay of different sequences or structural features has been found to be responsible for increased thermostability.13-15 As a unifying concept, it was suggested that these changes contribute to the improvement of the underlying network of noncovalent interactions within the structure, presumably leading to an overall increase in the mechanical stability/rigidity of the structure.16 At the same time, an appropriate distribution of —exible regions must be maintained in the thermostable protein because biological function and molecular motions are intimately linked.4,17