Does the active site of mammalian glutathione peroxidase (GPx) contain water molecules? An ONIOM study

Rajeev Prabhakar, Djamaladdin G. Musaev, Ilja V. Khavrutskii, Keiji Morokuma

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

In the present theoretical study, the active site of mammalian glutathione peroxidase (GPx) has been refined by including protein/active site interactions using the two-layer ONIOM(QM:MM) method. In this study, a full model consisting of 3113 atoms (with 86 active site atoms in the quantum mechanical (QM) region and the rest in the molecular mechanics (MM) region) has been constructed on the basis of the 2.9 Å resolution X-ray structure of mammalian GPx. The "active site only" models give much larger root-mean-square (rms) deviations from the X-ray structure than the full model, indicating the importance of the protein environment on the structure of the active site. The still substantial rms errors of the optimized structures can be improved only when the full model complemented with two water molecules is considered, clearly indicating the existence of two missing water molecules at the active site of the mammalian GPx, which could be critical for the catalytic activity.

Original languageEnglish (US)
Pages (from-to)12643-12645
Number of pages3
JournalJournal of Physical Chemistry B
Volume108
Issue number34
DOIs
StatePublished - Aug 26 2004
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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