THE STRUCTURE OF PYROCOCCUS-FURIOSUS GLUTAMATE-DEHYDROGENASE REVEALS A KEY ROLE FOR ION-PAIR NETWORKS IN MAINTAINING ENZYME STABILITY AT EXTREME TEMPERATURES

Background: The hyperthermophile Pyrococcus furiosus is one of the mos t thermostable organisms known, with an optimum growth temperature of 100 degrees C. The proteins from this organism display extreme thermos tability. We have undertaken the structure determination of glutamate dehydrogenase fi-om P. furiosus in order to gain further insights into the relationship between molecular structure and thermal stability. R esults: The structure of P. furiosus glutamate dehydrogenase, a homohe xameric enzyme, has been determined at 2.2 Angstrom resolution and com pared with the structure of glutamate dehydrogenase from the mesophile Clostridium symbiosum.Conclusions: Comparison of the structures of th ese two enzymes has revealed one major difference: the structure of th e hyperthermophilic enzyme contains a striking series of ion-pair netw orks on the surface of the protein subunits and buried at both interdo main and intersubunit interfaces. We propose that the formation of suc h extended networks may represent a major stabilizing feature associat ed with the adaptation of enzymes to extreme temperatures.