Structure and Reactivity of the Phosphotriesterase Active Site

Abstract

The structure and reactivity of the native, mutant, and metal substituted phosphotriesterase (PTE) is determined by ab initio quantum chemistry calculations. The x-ray structure for the Zn-Zn enzyme is leveraged into a catalytically competent active site in which a wide range of theoretical structures can be optimized for metal substituted and mutant active sites. The structural behavior of the active site is modeled using a new effective potential for representing the protein molecular environment (electrostatic, polarization, repulsive) interacting in the quantum Hamiltonian. The new methodology, effective fragment potentials (EFP), has been implemented in the GAMESS suite of electronic structure codes to make theoretical calculations on structure, spectroscopy, and reactivity tractable for systems involving many hundreds of atoms. Specific results on the structure of active site histidine to cysteine mutants, and a new proposal on the nucleophile for this hydrolase, will be presented.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2002
Accession Number
ADA436171

Entities

People

  • Morris Krauss

Tags

Communities of Interest

  • Energy and Power Technologies

DTIC Thesaurus Topics

  • Biomolecules
  • Chemical Reactions
  • Chemical Synthesis
  • Chemistry
  • Computational Chemistry Methods
  • Crystal Structure
  • Environment
  • Enzymes
  • Hydrogen Bonds
  • Hydrolysis
  • Inhibitors
  • Molecular Dynamics
  • Mutations
  • Quantum Chemistry
  • Substrates
  • Transitions
  • X Rays

Fields of Study

  • Chemistry

Readers

  • Molecular Photonics/Laser Physics
  • Molecular and Cellular Biochemistry

Technology Areas

  • Microelectronics
  • Quantum Computing