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Title: Mapping the Reaction Coordinates of Enzymatic Defluorination

Abstract

The carbon-fluorine bond is the strongest covalent bond in organic chemistry, yet fluoroacetate dehalogenases can readily hydrolyze this bond under mild physiological conditions. Elucidating the molecular basis of this rare biocatalytic activity will provide the fundamental chemical insights into how this formidable feat is achieved. Here, we present a series of high-resolution (1.15-1.80 {angstrom}) crystal structures of a fluoroacetate dehalogenase, capturing snapshots along the defluorination reaction: the free enzyme, enzyme-fluoroacetate Michaelis complex, glycolyl-enzyme covalent intermediate, and enzyme-product complex. We demonstrate that enzymatic defluorination requires a halide pocket that not only supplies three hydrogen bonds to stabilize the fluoride ion but also is finely tailored for the smaller fluorine halogen atom to establish selectivity toward fluorinated substrates. We have further uncovered dynamics near the active site which may play pivotal roles in enzymatic defluorination. These findings may ultimately lead to the development of novel defluorinases that will enable the biotransformation of more complex fluorinated organic compounds, which in turn will assist the synthesis, detoxification, biodegradation, disposal, recycling, and regulatory strategies for the growing markets of organofluorines across major industrial sectors.

Authors:
; ; ;  [1]
  1. (Toronto)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
FOREIGN
OSTI Identifier:
1023643
Resource Type:
Journal Article
Journal Name:
J. Am. Chem. Soc.
Additional Journal Information:
Journal Volume: 133; Journal Issue: (19) ; 05, 2011; Journal ID: ISSN 0002-7863
Country of Publication:
United States
Language:
ENGLISH
Subject:
08 HYDROGEN; ATOMS; BIODEGRADATION; CARBON; CHEMICAL BONDS; CRYSTAL STRUCTURE; DETOXIFICATION; DYNAMICS; ENZYMES; FLUORIDES; FLUORINE; HALIDES; HALOGENS; HYDROGEN; IONS; MAPPING; ORGANIC COMPOUNDS; RECYCLING; SUBSTRATES; SYNTHESIS

Citation Formats

Chan, Peter W.Y., Yakunin, Alexander F., Edwards, Elizabeth A., and Pai, Emil F. Mapping the Reaction Coordinates of Enzymatic Defluorination. United States: N. p., 2011. Web. doi:10.1021/ja200277d.
Chan, Peter W.Y., Yakunin, Alexander F., Edwards, Elizabeth A., & Pai, Emil F. Mapping the Reaction Coordinates of Enzymatic Defluorination. United States. doi:10.1021/ja200277d.
Chan, Peter W.Y., Yakunin, Alexander F., Edwards, Elizabeth A., and Pai, Emil F. Wed . "Mapping the Reaction Coordinates of Enzymatic Defluorination". United States. doi:10.1021/ja200277d.
@article{osti_1023643,
title = {Mapping the Reaction Coordinates of Enzymatic Defluorination},
author = {Chan, Peter W.Y. and Yakunin, Alexander F. and Edwards, Elizabeth A. and Pai, Emil F.},
abstractNote = {The carbon-fluorine bond is the strongest covalent bond in organic chemistry, yet fluoroacetate dehalogenases can readily hydrolyze this bond under mild physiological conditions. Elucidating the molecular basis of this rare biocatalytic activity will provide the fundamental chemical insights into how this formidable feat is achieved. Here, we present a series of high-resolution (1.15-1.80 {angstrom}) crystal structures of a fluoroacetate dehalogenase, capturing snapshots along the defluorination reaction: the free enzyme, enzyme-fluoroacetate Michaelis complex, glycolyl-enzyme covalent intermediate, and enzyme-product complex. We demonstrate that enzymatic defluorination requires a halide pocket that not only supplies three hydrogen bonds to stabilize the fluoride ion but also is finely tailored for the smaller fluorine halogen atom to establish selectivity toward fluorinated substrates. We have further uncovered dynamics near the active site which may play pivotal roles in enzymatic defluorination. These findings may ultimately lead to the development of novel defluorinases that will enable the biotransformation of more complex fluorinated organic compounds, which in turn will assist the synthesis, detoxification, biodegradation, disposal, recycling, and regulatory strategies for the growing markets of organofluorines across major industrial sectors.},
doi = {10.1021/ja200277d},
journal = {J. Am. Chem. Soc.},
issn = {0002-7863},
number = (19) ; 05, 2011,
volume = 133,
place = {United States},
year = {2011},
month = {9}
}