INSIGHTS INTO THE MOLECULAR-BASIS OF THERMAL-STABILITY FROM THE ANALYSIS OF ION-PAIR NETWORKS IN THE GLUTAMATE-DEHYDROGENASE FAMILY

The recent structure determination of glutamate dehydrogenase from the hyperthermophile Pyrococcus furiosus and the comparison of this struc ture with its counterparts from the mesophiles Clostridium symbiosum a nd Escherichia coli has highlighted the formation of extended networks of ion-pairs as a possible explanation for the superior thermal stabi lity of the hyperthermostable enzyme. in the light of this, we have ca rried out a homology-based modelling study using sequences of a range of glutamate dehydrogenases drawn from species which span a wide spect rum of optimal,growth temperatures. We have attempted to analyse the e xtent of the formation oi. ion-pair networks in these different enzyme s and tried to correlate this with the observed thermal stability. The results of this analysis indicate that the ion-pair networks become m ore fragmented as the temperature stability of the enzyme decreases an d are consistent with a role for the involvement of such networks in t he adaptation of enzymes to extreme temperatures.