To reveal the structural basis of the increased thermal stability of 3-isopropylmalate dehydrogenase (IPMDH) from Thermus thermophilus, an extreme thermophile, the homology-based structural model of one mesophilic (Escherichia coli) counterpart, was constructed. Both IPMDHs are homodimeric proteins. We built a model of one subunit using the 3-D structures of the Th. thermophilus IPMDH and the homologous E. coli isocitrate dehydrogenase. Energy minimization and molecular dynamics simulated annealing were performed on the dimer, including a surrounding solvation shell. No serious errors were detected in the refined model using the 3-D profile method. The resulting structure was scrutinized and compared with the structure of the Th. thermophilus IPMDH. Significant differences were found in the non-specific interactions including the hydrophobic effect. The model predicts a higher number of ion pairs in the Th. thermophilus than in the E. coli enzyme. An increase was observed in the stabilities of α-helical regions in the thermophilic protein. The preliminary X-ray coordinates of the E. coli IPMDH were received after the completion of this work, allowing an assessment of the mode! in terms of the X-ray structure. The comparison proved that most of the structural features underlying the stability differences between the two enzymes were predicted correctly.
|Number of pages||8|
|Publication status||Published - Aug 1 1996|
- 3-isopropylmalate dehydrogenase
- Homology modeling
- Protein structure prediction
ASJC Scopus subject areas
- Molecular Biology