Docking of 4-oxalocrotonate tautomerase substrates: Implications for the catalytic mechanism

T. A. Soares, D. S. Goodsell, J. M. Briggs, R. Ferreira, A. J. Olson

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The enzyme 4-oxalocrotonate tautomerase catalyzes the ketonization of dienols, which after further processing become intermediates in the Krebs cycle. The enzyme uses a general acid-base mechanism for proton transfer: the amino-terminal proline has been shown to function as the catalytic base and Arg39 has been implicated as the catalytic acid. We report the results of molecular docking simulations of 4-oxalocrotonate tautomerase with two substrates, 2-hydroxymuconate and 5-carboxymethyl-2-hydroxymuconate. pK(a) calculations are also performed for the free enzyme. The predicted binding mode of 2-hydroxymuconate is in agreement with experimental data. A model for the binding mode of 5-carboxymethyl-2-hydroxymuconate is proposed which explains the lower catalytic efficiency of the enzyme toward this substrate. The pK(a) predictions and docking simulations support residue Arg39 as the general acid for the enzyme catalysis.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
Issue number3
StatePublished - Sep 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry


  • 4-oxalocrotonate tautomerase
  • Catalytic mechanism
  • Molecular docking
  • pK(a) predictions


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