Fluorescently Labelled ATP Analogues for Direct Monitoring of Ubiquitin Activation.


Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
15 May 2020
Historique:
received: 02 03 2020
revised: 06 03 2020
pubmed: 11 3 2020
medline: 19 8 2020
entrez: 11 3 2020
Statut: ppublish

Résumé

Simple and robust assays to monitor enzymatic ATP cleavage with high efficiency in real-time are scarce. To address this shortcoming, we developed fluorescently labelled adenosine tri-, tetra- and pentaphosphate analogues of ATP. The novel ATP analogues bear - in contrast to earlier reports - only a single acridone-based dye at the terminal phosphate group. The dye's fluorescence is quenched by the adenine component of the ATP analogue and is restored upon cleavage of the phosphate chain and dissociation of the dye from the adenosine moiety. Thereby the activity of ATP-cleaving enzymes can be followed in real-time. We demonstrate this proficiency for ubiquitin activation by the ubiquitin-activating enzymes UBA1 and UBA6 which represents the first step in an enzymatic cascade leading to the covalent attachment of ubiquitin to substrate proteins, a process that is highly conserved from yeast to humans. We found that the efficiency to serve as cofactor for UBA1/UBA6 very much depends on the length of the phosphate chain of the ATP analogue: triphosphates are used poorly while pentaphosphates are most efficiently processed. Notably, the novel pentaphosphate-harbouring ATP analogue supersedes the efficiency of recently reported dual-dye labelled analogues and thus, is a promising candidate for broad applications.

Identifiants

pubmed: 32154932
doi: 10.1002/chem.202001091
pmc: PMC7317923
doi:

Substances chimiques

Fluorescent Dyes 0
UBA6 protein, human 0
Adenosine Triphosphate 8L70Q75FXE
Ubiquitin-Activating Enzymes EC 6.2.1.45

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

6279-6284

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 969

Informations de copyright

© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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Auteurs

Daniel Hammler (D)

Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.

Katrin Stuber (K)

Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.
Department of Biology, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.

Fabian Offensperger (F)

Department of Biology, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.

Martin Scheffner (M)

Department of Biology, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.

Andreas Zumbusch (A)

Department of Chemistry and Center for Applied Photonics, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.

Andreas Marx (A)

Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.

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Classifications MeSH