Sequence similarity of mammalian epoxide hydrolases to the bacterial haloalkane dehalogenase and other related proteins. Implication for the potential catalytic mechanism of enzymatic epoxide hydrolysis

Michael Arand, David F. Grant, Jeffrey K. Beetham, Thomas Friedberg, Franz Oesch, Bruce D. Hammock

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Direct comparison of the amino acid sequences of microsomal and soluble epoxide hydrolase superficially indicates that these enzymes are unrelated. Both proteins, however, share significant sequence similarity to a bacterial haloalkane dehalogenase that has earlier been shown to belong to the α/β hydrolase fold family of enzymes. The catalytic mechanism for the dehalogenase has been elucidated in detail [Verschueren et al. (1993) Nature 363, 693-698] and proceeds via an ester intermediate where the substrate is covalently bound to the enzyme. From these observations we conclude (i) that microsomal and soluble epoxide hydrolase are distantly related enzymes that have evolved from a common ancestral protein together with the haloalkane dehalogenase and a variety of other proteins specified in the present paper, (ii) that these enzymes most likely belong to the α/β hydrolase fold family of enzymes and (iii) that the enzymatic epoxide hydrolysis proceeds via a hydroxy ester intermediate, in contrast to the presently favoured base-catalyzed direct attack of the epoxide by an activated water.

Original languageEnglish (US)
Pages (from-to)251-256
Number of pages6
JournalFEBS Letters
Volume338
Issue number3
DOIs
StatePublished - Feb 7 1994

    Fingerprint

Keywords

  • Chelatase
  • Esterase
  • Hydrolase
  • Lipase
  • Luciferase
  • Peroxidase
  • α/β Hydrolase fold

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this