INSIGHTS INTO THE MOLECULAR-BASIS OF THERMAL-STABILITY FROM THE STRUCTURE DETERMINATION OF PYROCOCCUS-FURIOSUS GLUTAMATE-DEHYDROGENASE

The structure determination of the glutamate dehydrogenase from the hy perthermophile Pyrococcus furiosus has been completed at 2.2 Angstrom resolution. The structure has been compared with the glutamate dehydro genases from the mesophiles Clostridium symbiosum, Escherichia coli an d Neurospora crassa. This comparison has revealed that the hyperthermo philic enzyme contains a striking series of networks of ion-pairs whic h are formed by regions of the protein which contain a high density of charged residues. Such regions are not found in the mesophilic enzyme s and the number and extent of ion-pair formation is much more limited . The ion-pail networks are clustered at both inter domain and inter s ubunit interfaces and may well represent a major stabilising feature a ssociated with the adaptation of enzymes to extreme temperatures.