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 structure with its counterparts from the mesophiles Clostridium symbiosum and Escherichia coli has highlighted the formation of extended networks of ion-pairs as a possible explanation for the superior thermal stability of the hyperthermostable enzyme. In the light of this, we have carried out a homology-based modelling study using sequences of a range of glutamate dehydrogenases drawn from species which span a wide spectrum of optimal growth temperatures. We have attempted to analyse the extent of the formation of ion-pair networks in these different enzymes and tried to correlate this with the observed thermal stability. The results of this analysis indicate that the ion-pair networks become more fragmented as the temperature stability of the enzyme decreases and are consistent with a role for the involvement of such networks in the adaptation of enzymes to extreme temperatures.
The Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
K S
KS
Yip
K L
KL
Britton
T J
TJ
Stillman
J
J
Lebbink
W M
WM
de Vos
F T
FT
Robb
C
C
Vetriani
D
D
Maeder
D W
DW
Rice
D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology; D003013:Clostridium / Q000201:enzymology; D003198:Computer Simulation; D004795:Enzyme Stability; D004926:Escherichia coli / Q000201:enzymology; D005969:Glutamate Dehydrogenase / Q000737:chemistry*; D006358:Hot Temperature; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software; D013816:Thermodynamics
D046911:Macromolecular Substances; D005969:Glutamate Dehydrogenase