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Related Experiment Videos

Nitric oxide binding to ferric cytochrome P450: a computational study.

D A Scherlis1, C B Cymeryng, D A Estrin

  • 1Departamento de Química Inorgánica, Analítica y Química-Física and INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria-Pab II, 1428 Buenos Aires, Argentina.

Inorganic Chemistry
|January 16, 2003
PubMed
Summary

Nitric oxide (NO) interaction with ferric cytochrome P450 active sites was studied. The ligand exchange reaction is thermodynamically feasible, providing insights into enzyme inhibition mechanisms.

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Area of Science:

  • Biochemistry
  • Computational Chemistry
  • Enzymology

Background:

  • Ferric cytochrome P450 enzymes are crucial in metabolism.
  • Nitric oxide (NO) is known to inhibit these enzymes.
  • Understanding NO interaction with the active site is key to elucidating inhibition mechanisms.

Purpose of the Study:

  • To investigate the interaction between nitric oxide and the ferric cytochrome P450 active site.
  • To analyze the thermodynamic feasibility of NO substituting a water molecule in the active site.
  • To explore the electronic properties and spin states of the nitrosylated complex.

Main Methods:

  • Density Functional Theory (DFT) at the generalized gradient approximation level.
  • SAM1 semiempirical method.

Related Experiment Videos

  • Hybrid quantum classical approach to include protein electrostatic effects.
  • Active-site modeling with iron(III) porphyrin, cysteine, and water.

    • Main Results:

    • Unpaired electron density, HOMO, and LUMO are localized on iron and coordinated sulfur.
    • Ligand exchange of H2O by NO is exergonic in both vacuum and protein environments.
    • A low-spin ground state with a linear Fe-N-O angle was obtained for the nitrosyl complex.

    Conclusions:

    • The electronic localization provides insight into NO reactivity with the active site.
    • The ligand exchange reaction is thermodynamically favorable, supporting the proposed inhibition mechanism.
    • Protein electrostatic fields significantly affect computed properties, but relative spin state orders remain consistent.