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Evaluating the potential for halogen bonding in the oxyanion hole of ketosteroid isomerase using unnatural amino acid mutagenesis

Academic Article
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Overview

authors

  • Kraut, D. A.
  • Churchill, Michael Jerome
  • Dawson, Philip
  • Herschlag, D.

publication date

  • April 2009

journal

  • ACS Chemical Biology  Journal

abstract

  • There has recently been an increasing interest in controlling macromolecular conformations and interactions through halogen bonding. Halogen bonds are favorable electrostatic interactions between polarized, electropositive chlorine, bromine, or iodine atoms and electronegative atoms such as oxygen or nitrogen. These interactions have been likened to hydrogen bonds in terms of their favored acceptor molecules, their geometries, and their energetics. We asked whether a halogen bond could replace a hydrogen bond in the oxyanion hole of ketosteroid isomerase, using semisynthetic enzymes containing para-halogenated phenylalanine derivatives to replace the tyrosine hydrogen bond donor. Formation of a halogen bond to the oxyanion in the transition state would be expected to rescue the effects of mutation to phenylalanine, but all of the halogenated enzymes were comparable in activity to the phenylalanine mutant. We conclude that, at least in this active site, a halogen bond cannot functionally replace a hydrogen bond.

subject areas

  • Amino Acid Sequence
  • Anions
  • Binding Sites
  • Hydrocarbons, Halogenated
  • Hydrogen
  • Mutagenesis, Site-Directed
  • Oxygen
  • Steroid Isomerases
  • Tyrosine
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Identity

PubMed Central ID

  • PMC2708088

International Standard Serial Number (ISSN)

  • 1554-8929

Digital Object Identifier (DOI)

  • 10.1021/cb900016q

PubMed ID

  • 19260691
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Additional Document Info

start page

  • 269

end page

  • 273

volume

  • 4

issue

  • 4

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