3R3U

Crystal Structure of the Fluoroacetate Dehalogenase RPA1163 - WT/apo

Summary for 3R3U

• Entry DOI: 10.2210/pdb3r3u/pdb
• Related: 3R3V 3R3W 3R3X 3R3Y 3R3Z 3R40 3R41
• Descriptor: Fluoroacetate dehalogenase, NICKEL (II) ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: facd, defluorinase, alpha/beta hydrolase, hydrolase
• Biological source: Rhodopseudomonas palustris
• Total number of polymer chains: 4
• Total formula weight: 136612.53

Authors

Chan, P.W.Y.,Yakunin, A.F.,Edwards, E.A.,Pai, E.F. (deposition date: 2011-03-16, release date: 2011-05-04, Last modification date: 2024-02-21)

Primary citation

Chan, P.W.,Yakunin, A.F.,Edwards, E.A.,Pai, E.F.
Mapping the reaction coordinates of enzymatic defluorination.
J.Am.Chem.Soc., 133:7461-7468, 2011

PubMed 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 Å) 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.

PubMed: 21510690
DOI: 10.1021/ja200277d

Experimental method

X-RAY DIFFRACTION (1.6 Å)