Redox-dependent substrate-cofactor interactions in the Michaelis-complex of a flavin-dependent oxidoreductase

Tobias Werther, Stefan Wahlefeld, Johannes Salewski, Uwe Kuhlmann, Ingo Zebger, Peter Hildebrandt () and Holger Dobbek ()
Additional contact information
Tobias Werther: Institut für Biologie, Strukturbiologie/Biochemie, Humboldt-Universität zu Berlin
Stefan Wahlefeld: Technische Universität Berlin, Institut für Chemie
Johannes Salewski: Technische Universität Berlin, Institut für Chemie
Uwe Kuhlmann: Technische Universität Berlin, Institut für Chemie
Ingo Zebger: Technische Universität Berlin, Institut für Chemie
Peter Hildebrandt: Technische Universität Berlin, Institut für Chemie
Holger Dobbek: Institut für Biologie, Strukturbiologie/Biochemie, Humboldt-Universität zu Berlin

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract How an enzyme activates its substrate for turnover is fundamental for catalysis but incompletely understood on a structural level. With redox enzymes one typically analyses structures of enzyme–substrate complexes in the unreactive oxidation state of the cofactor, assuming that the interaction between enzyme and substrate is independent of the cofactors oxidation state. Here, we investigate the Michaelis complex of the flavoenzyme xenobiotic reductase A with the reactive reduced cofactor bound to its substrates by X-ray crystallography and resonance Raman spectroscopy and compare it to the non-reactive oxidized Michaelis complex mimics. We find that substrates bind in different orientations to the oxidized and reduced flavin, in both cases flattening its structure. But only authentic Michaelis complexes display an unexpected rich vibrational band pattern uncovering a strong donor–acceptor complex between reduced flavin and substrate. This interaction likely activates the catalytic ground state of the reduced flavin, accelerating the reaction within a compressed cofactor–substrate complex.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms16084 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16084

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms16084

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().