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Catabolic reductive dehalogenase substrate complex structures underpin rational repurposing of substrate scope

DOI: 10.3390/microorganisms8091344 DOI Help

Authors: Tom Halliwell (Manchester Institute of Biotechnology, University of Manchester) , Karl Fisher (Manchester Institute of Biotechnology) , Karl A. P. Payne (Manchester Institute of Biotechnology, University of Manchester) , Stephen E. J. Rigby (Manchester Institute of Biotechnology, University of Manchester) , David Leys (Manchester Institute of Biotechnology, University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Microorganisms , VOL 8

State: Published (Approved)
Published: September 2020
Diamond Proposal Number(s): 12788 , 17773

Open Access Open Access

Abstract: Reductive dehalogenases are responsible for the reductive cleavage of carbon-halogen bonds during organohalide respiration. A variety of mechanisms have been proposed for these cobalamin and [4Fe-4S] containing enzymes, including organocobalt, radical, or cobalt-halide adduct based catalysis. The latter was proposed for the oxygen-tolerant Nitratireductor pacificus pht-3B catabolic reductive dehalogenase (NpRdhA). Here, we present the first substrate bound NpRdhA crystal structures, confirming a direct cobalt–halogen interaction is established and providing a rationale for substrate preference. Product formation is observed in crystallo due to X-ray photoreduction. Protein engineering enables rational alteration of substrate preference, providing a future blue print for the application of this and related enzymes in bioremediation.

Journal Keywords: reductive dehalogenase; cobalamin; iron-sulphur clusters; bioremediation; EPR; X-ray crystallography

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)