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Theoretical Chemistry Accounts

, Volume 105, Issue 3, pp 207–212 | Cite as

Transition structure selectivity in enzyme catalysis: a QM/MM study of chorismate mutase

  • Sergio Martí
  • Juan Andrés
  • Vicent Moliner
  • Estanislao Silla
  • Iñaki Tuñón
  • Juan Bertrán
Regular article

Abstract.

Two different transition structures (TSs) have been located and characterized for the chorismate conversion to prephenate in Bacillus subtilis chorismate mutase by means of hybrid quantum-mechanical/molecular-mechanical (QM/MM) calculations. GRACE software, combined with an AM1/CHARMM24/TIP3P potential, has been used involving full gradient relaxation of the position of ca. 3300 atoms. These TSs have been connected with their respective reactants and products by the intrinsic reaction coordinate (IRC) procedure carried out in the presence of the protein environment, thus obtaining for the first time a realistic enzymatic reaction path for this reaction. Similar QM/MM computational schemes have been applied to study the chemical reaction solvated by ca. 500 water molecules. Comparison of these results together with gas phase calculations has allowed understanding of the catalytic efficiency of the protein. The enzyme stabilizes one of the TSs (TSOHout) by means of specific hydrogen bond interactions, while the other TS (TSOHin) is the preferred one in vacuum and in water. The enzyme TS is effectively more polarized but less dissociative than the corresponding solvent and gas phase TSs. Electrostatic stabilization and an intramolecular charge-transfer process can explain this enzymatically induced change. Our theoretical results provide new information on an important enzymatic transformation and the key factors responsible for efficient selectivity are clarified.

Key words: Chorismate mutase Rearrangement Enzyme catalysis Ab initio calculations Quantum mechanics-molecular mechanics 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Sergio Martí
    • 1
  • Juan Andrés
    • 1
  • Vicent Moliner
    • 1
  • Estanislao Silla
    • 2
  • Iñaki Tuñón
    • 2
  • Juan Bertrán
    • 3
  1. 1. Departament de Ciències Experimentals, Universitat Jaume I, Box 224, 12080 Castellón, Spain e-mail: moliner@exp.uji.es, Fax: +34-964-728066ES
  2. 2. Departament de Química Física, Universidad de Valencia, 46100 Burjasot, Valencia, Spain e-mail: ignacio.tunon@uv.es, Fax: +34-963-864564ES
  3. 3. Departament de Química, Universidad Autónoma de Barcelona, 08193 Bellaterra, Barcelona, SpainES

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