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Infrared spectroscopy elucidates the inhibitor binding sites in a metal-dependent formate dehydrogenase
Citation Link: https://doi.org/10.15480/882.4647
Publikationstyp
Journal Article
Date Issued
2022-06-05
Sprache
English
Institut
TORE-DOI
Journal
Volume
28
Issue
54
Article Number
e202201091
Citation
Chemistry - A European Journal 28 (54): e202201091 (2022-09-27)
Publisher DOI
Scopus ID
Publisher
Wiley-VCH
Biological carbon dioxide (CO2) reduction is an important step by which organisms form valuable energy-richer molecules required for further metabolic processes. The Mo-dependent formate dehydrogenase (FDH) from Rhodobacter capsulatus catalyzes reversible formate oxidation to CO2 at a bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor. To elucidate potential substrate binding sites relevant for the mechanism, we studied herein the interaction with the inhibitory molecules azide and cyanate, which are isoelectronic to CO2 and charged as formate. We employed infrared (IR) spectroscopy in combination with density functional theory (DFT) and inhibition kinetics. One distinct inhibitory molecule was found to bind to either a non-competitive or a competitive binding site in the secondary coordination sphere of the active site. Site-directed mutagenesis of key amino acid residues in the vicinity of the bis-MGD cofactor revealed changes in both non-competitive and competitive binding, whereby the inhibitor is in case of the latter interaction presumably bound between the cofactor and the adjacent Arg587.
Subjects
CO reduction 2
DFT
formate oxidation
inhibition kinetics
IR spectroscopy
molybdoenzyme
DDC Class
540: Chemie
600: Technik
Publication version
publishedVersion
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Chemistry A European J - 2022 - Laun - Infrared Spectroscopy Elucidates the Inhibitor Binding Sites in a Metal_u2010Dependent.pdf
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