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

✍ Scribed by T. A. Soares; D. S. Goodsell; J. M. Briggs; R. Ferreira; A. J. Olson

Publisher: Wiley (John Wiley & Sons)
Year: 1999
Tongue: English
Weight: 194 KB
Volume: 50
Category: Article
ISSN: 0006-3525
DOI: 10.1002/(sici)1097-0282(199909)50:3<319::aid-bip7>3.0.co;2-8

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✦ Synopsis

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.

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