Relationship between thermal stability and 3-D structure in a homology model of 3-isopropylmalate dehydrogenase from Escherichia coli

C. Magyar, András Szilágyi, P. Závodszky

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)663-670
Number of pages8
JournalProtein Engineering
Volume9
Issue number8
Publication statusPublished - Aug 1996

Fingerprint

3-Isopropylmalate Dehydrogenase
Thermus thermophilus
Escherichia coli
Thermodynamic stability
Hot Temperature
X-Rays
Isocitrate Dehydrogenase
X rays
Enzymes
Structural Models
Solvation
Proteins
Molecular Dynamics Simulation
Simulated annealing
Hydrophobic and Hydrophilic Interactions
Dimers
Molecular dynamics
Ions
Oxidoreductases

Keywords

  • 3-isopropylmalate dehydrogenase
  • Homology modeling
  • Protein structure prediction
  • Thermophiles
  • Thermostability

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

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title = "Relationship between thermal stability and 3-D structure in a homology model of 3-isopropylmalate dehydrogenase from Escherichia coli",
abstract = "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.",
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AU - Szilágyi, András

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N2 - 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.

AB - 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.

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