Substrate orientation in 4-oxalocrotonate tautomerase and its effect on QM/MM energy profiles

T. Tuttle, W. Thiel

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The tautomerization of 2-oxo-4E-hexendioate by 4-oxalocrotonate tautomerase has been studied by quantum mechanical/molecular mechanical (QM/MM) methods using three models, A−C, with different substrate orientations. The computed QM/MM energy profiles are rather different. Various energy partitioning analyses indicate the origin of these differences and the role of the active site residues for different substrate orientations. The proposed new model C is preferred over the previously used models A and B because it combines favorable substrate binding geometries with reasonable barriers and is consistent with the experimental evidence from mutation studies concerning the catalytic ability of specific residues in the binding site, especially R11‘.
Original languageEnglish
Pages (from-to)7665-7674
Number of pages10
JournalJournal of Physical Chemistry B
Issue number26
Publication statusPublished - 14 Jun 2007



  • quantum mechanical
  • molecular mechanical
  • energy profiles
  • energy partitioning analyses
  • substrate binding geometries

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