Understanding the enzymatic activity of 4-oxalocrotonate tautomerase and its mutant analogues: a computational study

Tell Tuttle, Ehud Keinan, Walter Thiel

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7 Citations (Scopus)

Abstract

The effect of replacing arginine residues (Arg) with citrulline residues (Cit) in the binding site of 4-oxalocrotonate tautomerase (4-OT) was investigated with force field molecular dynamics and hybrid quantum mechanics/molecular mechanics studies. It is found that the Arg61Cit mutation has only minor effects on the kcat and KM values determined experimentally because of the flexibility of this residue. The decrease in kcat and increase in KM for the Arg11Cit and Arg39Cit mutations are due to the disruption of the binding site, which arises from repulsive interactions with neighboring residues. The results of this investigation shed new light on the effects of mutations in the binding site of 4-OT and consequently on how the enzyme binds the active substrate.

Original languageEnglish
Pages (from-to)19685-19695
Number of pages11
JournalJournal of Physical Chemistry B
Volume110
Issue number39
Early online date13 Sep 2006
DOIs
Publication statusPublished - 5 Oct 2006

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Keywords

  • force field molecular dynamics
  • binding
  • mutations
  • enzymes

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