4RAS

Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation

Summary for 4RAS

• Entry DOI: 10.2210/pdb4ras/pdb
• Descriptor: Oxidoreductase, NAD-binding/iron-sulfur cluster-binding protein, IRON/SULFUR CLUSTER, COBALAMIN, ... (6 entities in total)
• Functional Keywords: ferrodoxin and cobalamin-binding domain, reductive dehalogenase, iron sulfur binding, cobalamin binding, oxidoreductase
• Biological source: Nitratireductor pacificus pht-3B
• Total number of polymer chains: 3
• Total formula weight: 238575.52

Authors

Quezada, C.P.,Payne, K.A.P.,Leys, D. (deposition date: 2014-09-11, release date: 2014-10-15, Last modification date: 2024-02-28)

Primary citation

Payne, K.A.,Quezada, C.P.,Fisher, K.,Dunstan, M.S.,Collins, F.A.,Sjuts, H.,Levy, C.,Hay, S.,Rigby, S.E.,Leys, D.
Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation.
Nature, 517:513-516, 2015

PubMed 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.

PubMed: 25327251
DOI: 10.1038/nature13901

Experimental method

X-RAY DIFFRACTION (2.3 Å)