Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation

Karl A P Payne, Carolina P. Quezada, Karl Fisher, Mark S. Dunstan, Fraser A. Collins, Hanno Sjuts, Colin Levy, Sam Hay, Stephen E J Rigby, David Leys

Resultado de la investigación: Article

135 Citas (Scopus)

Resumen

Organohalide chemistry underpins many industrial and agricultural processes, and a large proportion of environmental pollutants are organohalides. Nevertheless, organohalide chemistry is not exclusively of anthropogenic origin, with natural abiotic and biological processes contributing to the global halide cycle. Reductive dehalogenases are responsible for biological dehalogenation in organohalide respiring bacteria, with substrates including polychlorinated biphenyls or dioxins. Reductive dehalogenases form a distinct subfamily of cobalamin (B12)-dependent enzymes that are usually membrane associated and oxygen sensitive, hindering detailed studies. 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 subfamilies, 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.

Idioma originalEnglish
Páginas (desde-hasta)513-516
Número de páginas4
PublicaciónNature
Volumen517
N.º7535
DOI
EstadoPublished - 22 ene 2015

Huella dactilar

Vitamin B 12
Cobalt
Halogens
Biocatalysis
Oxygen
Biological Phenomena
Environmental Pollutants
Environmental Biodegradation
Dioxins
Polychlorinated Biphenyls
Electron Spin Resonance Spectroscopy
Enzymes
Catalysis
Spectrum Analysis
Carbon
Bacteria
Membranes

ASJC Scopus subject areas

  • General

Citar esto

Payne, K. A. P., Quezada, C. P., Fisher, K., Dunstan, M. S., Collins, F. A., Sjuts, H., ... Leys, D. (2015). Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation. Nature, 517(7535), 513-516. https://doi.org/10.1038/nature13901
Payne, Karl A P ; Quezada, Carolina P. ; Fisher, Karl ; Dunstan, Mark S. ; Collins, Fraser A. ; Sjuts, Hanno ; Levy, Colin ; Hay, Sam ; Rigby, Stephen E J ; Leys, David. / Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation. En: Nature. 2015 ; Vol. 517, N.º 7535. pp. 513-516.
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abstract = "Organohalide chemistry underpins many industrial and agricultural processes, and a large proportion of environmental pollutants are organohalides. Nevertheless, organohalide chemistry is not exclusively of anthropogenic origin, with natural abiotic and biological processes contributing to the global halide cycle. Reductive dehalogenases are responsible for biological dehalogenation in organohalide respiring bacteria, with substrates including polychlorinated biphenyls or dioxins. Reductive dehalogenases form a distinct subfamily of cobalamin (B12)-dependent enzymes that are usually membrane associated and oxygen sensitive, hindering detailed studies. 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 subfamilies, 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.",
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Payne, KAP, Quezada, CP, Fisher, K, Dunstan, MS, Collins, FA, Sjuts, H, Levy, C, Hay, S, Rigby, SEJ & Leys, D 2015, 'Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation', Nature, vol. 517, n.º 7535, pp. 513-516. https://doi.org/10.1038/nature13901

Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation. / Payne, Karl A P; Quezada, Carolina P.; Fisher, Karl; Dunstan, Mark S.; Collins, Fraser A.; Sjuts, Hanno; Levy, Colin; Hay, Sam; Rigby, Stephen E J; Leys, David.

En: Nature, Vol. 517, N.º 7535, 22.01.2015, p. 513-516.

Resultado de la investigación: Article

TY - JOUR

T1 - Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation

AU - Payne, Karl A P

AU - Quezada, Carolina P.

AU - Fisher, Karl

AU - Dunstan, Mark S.

AU - Collins, Fraser A.

AU - Sjuts, Hanno

AU - Levy, Colin

AU - Hay, Sam

AU - Rigby, Stephen E J

AU - Leys, David

PY - 2015/1/22

Y1 - 2015/1/22

N2 - Organohalide chemistry underpins many industrial and agricultural processes, and a large proportion of environmental pollutants are organohalides. Nevertheless, organohalide chemistry is not exclusively of anthropogenic origin, with natural abiotic and biological processes contributing to the global halide cycle. Reductive dehalogenases are responsible for biological dehalogenation in organohalide respiring bacteria, with substrates including polychlorinated biphenyls or dioxins. Reductive dehalogenases form a distinct subfamily of cobalamin (B12)-dependent enzymes that are usually membrane associated and oxygen sensitive, hindering detailed studies. 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 subfamilies, 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.

AB - Organohalide chemistry underpins many industrial and agricultural processes, and a large proportion of environmental pollutants are organohalides. Nevertheless, organohalide chemistry is not exclusively of anthropogenic origin, with natural abiotic and biological processes contributing to the global halide cycle. Reductive dehalogenases are responsible for biological dehalogenation in organohalide respiring bacteria, with substrates including polychlorinated biphenyls or dioxins. Reductive dehalogenases form a distinct subfamily of cobalamin (B12)-dependent enzymes that are usually membrane associated and oxygen sensitive, hindering detailed studies. 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 subfamilies, 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.

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U2 - 10.1038/nature13901

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M3 - Article

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AN - SCOPUS:84925494212

VL - 517

SP - 513

EP - 516

JO - Nature

JF - Nature

SN - 0028-0836

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Payne KAP, Quezada CP, Fisher K, Dunstan MS, Collins FA, Sjuts H y otros. Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation. Nature. 2015 ene 22;517(7535):513-516. https://doi.org/10.1038/nature13901