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Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation

DOI: 10.1038/nature13901 DOI Help
PMID: 25327251 PMID Help

Authors: Karl Payne (University of Manchester) , Carolina Quezada (University of Manchester) , Karl Fisher (Manchester Institute of Biotechnology) , Mark Dunstan (University of Manchester) , Fraser A. Collins (University of Manchester) , Hanno Sjuts (University of Manchester) , Colin Levy (School of Chemistry & Manchester Interdisciplinary Biocentre, The University of Manchester) , Sam Hay (University of Manchester) , Stephen E. J. Rigby (University of Manchester) , David Leys (School of Chemistry & Manchester Interdisciplinary Biocentre, The University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 517 (7535) , PAGES 513 - 516

State: Published (Approved)
Published: October 2014
Diamond Proposal Number(s): 8997

Open Access Open Access

Abstract: Organohalide chemistry underpins many industrial and agricultural processes, and a large proportion of environmental pollutants are organohalides1. Nevertheless, organohalide chemistry is not exclusively of anthropogenic origin, with natural abiotic and biological processes contributing to the global halide cycle2, 3. Reductive dehalogenases are responsible for biological dehalogenation in organohalide respiring bacteria4, 5, with substrates including polychlorinated biphenyls or dioxins6, 7. Reductive dehalogenases form a distinct subfamily of cobalamin (B12)-dependent enzymes that are usually membrane associated and oxygen sensitive, hindering detailed studies8, 9, 10, 11, 12. Here we report the characterization of a soluble, oxygen-tolerant reductive dehalogenase and, by combining structure determination with EPR (electron paramagnetic resonance) spectroscopy and simulation, show that a direct interaction between the cobalamin cobalt and the substrate halogen underpins catalysis. In contrast to the carbon–cobalt bond chemistry catalysed by the other cobalamin-dependent subfamilies13, we propose that reductive dehalogenases achieve reduction of the organohalide substrate via halogen–cobalt bond formation. This presents a new model in both organohalide and cobalamin (bio)chemistry that will guide future exploitation of these enzymes in bioremediation or biocatalysis.

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I04-Macromolecular Crystallography