Catalytic mechanism and metal specificity of bacterial peptide deformylase: A density functional theory QM/MM study

Chuanyun Xiao, Yingkai Zhang

Research output: Contribution to journalArticle

Abstract

Bacterial peptide deformylase (PDF) represents a novel class of mononuclear iron peptidase, and has an intriguing metal preference different from most other metalloproteases. Using a hybrid density functional theory (B3LYP) QM/MM method, we have theoretically investigated its catalytic mechanism and metal specificity by studying both Fe2+-PDF and Zn2+-PDF. In both forms of PDF, the conserved Glu133 residue is protonated in the reactant complex, and acts as a general acid during the reaction. The initial reaction step is the nucleophilic attack of the metal-bound hydroxide on the carbonyl carbon of the substrate. Our calculations indicate that the metal ion in Fe 2+-PDF is always pentacoordinated during the reaction process, while that in Zn2+-PDF is only tetrahedrally coordinated and not bound to the substrate in the reactant complex. This difference in their metal coordination is suggested to account for the lower activity of Zn 2+-PDF in comparison with Fe2+-PDF.

Original languageEnglish (US)
Pages (from-to)6229-6235
Number of pages7
JournalJournal of Physical Chemistry B
Volume111
Issue number22
DOIs
StatePublished - Jun 7 2007

ASJC Scopus subject areas

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

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