Enzymes that catalyse S(N)2 reaction mechanisms

David O'Hagan*, Jason W. Schmidberger

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

37 Citations (Scopus)

Abstract

Enzymes have evolved to catalyse reactions, reducing the activation barrier by lowering transition state energy. Many reaction types are represented in enzymology; however, it is noticeable that S(N)2-type nucleophilic reactions at carbon are not common. The activation barrier of an S(N)2 reaction is generally high, as it progresses through a trigonal bipyramidal transition state, and this presents a challenge to efficient catalysis. This review summarises those enzyme reactions which almost certainly take place by a S(N)2 reaction mechanism, although it is recognised that the S(N)2 terminology, which derives from the bimolecular kinetics of a reaction in solution, is compromised to some extent in enzymes as they all display Michealis-Menten kinetics. Nonetheless, the S(N)2 terminology is used here to classify enzymes which catalyse nucleophilic reactions at sp(3)-hybridised carbon. There is a particular focus on highlighting the active-site residues involved in catalysis where known, information that comes primarily from a combination of structural and mutagenesis studies. Predictably, methyl transfer reactions are most widely represented; however, there are a number of enzymes that halogenate/dehalogenate, as well as epoxide hydrolases and inverting sulfatases. Although most of the enzymes have been known for some time, recent advances in structural biology are providing more details on how such enzymes function.

Original languageEnglish
Pages (from-to)900-918
Number of pages19
JournalNatural Product Reports
Volume27
Issue number6
DOIs
Publication statusPublished - 2010

Keywords

  • FLUOROACETATE DEHALOGENASE
  • L-2-HALOACID DEHALOGENASE
  • HALOALKANE DEHALOGENASE LINB
  • XANTHOBACTER-AUTOTROPHICUS GJ10
  • HALOACID DEHALOGENASE
  • SITE-DIRECTED MUTAGENESIS
  • CHIRAL METHYL-GROUPS
  • AGROBACTERIUM-RADIOBACTER AD1
  • CRYSTAL-STRUCTURE
  • SPHINGOMONAS-PAUCIMOBILIS UT26

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