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

T. Tuttle, W. Thiel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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‘.
LanguageEnglish
Pages7665-7674
Number of pages10
JournalJournal of Physical Chemistry B
Volume111
Issue number26
DOIs
Publication statusPublished - 14 Jun 2007

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Substrates
profiles
Binding sites
mutations
energy
Binding Sites
Geometry
geometry
4-oxalocrotonate tautomerase

Keywords

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

Cite this

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abstract = "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‘.",
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Substrate orientation in 4-oxalocrotonate tautomerase and its effect on QM/MM energy profiles. / Tuttle, T.; Thiel, W.

In: Journal of Physical Chemistry B, Vol. 111, No. 26, 14.06.2007, p. 7665-7674.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Substrate orientation in 4-oxalocrotonate tautomerase and its effect on QM/MM energy profiles

AU - Tuttle, T.

AU - Thiel, W.

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N2 - 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‘.

AB - 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‘.

KW - quantum mechanical

KW - molecular mechanical

KW - energy profiles

KW - energy partitioning analyses

KW - substrate binding geometries

U2 - 10.1021/jp0685986

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