Evolutionary and molecular basis of ADP-ribosylation reversal by zinc-dependent macrodomains.

Autor:	Ariza A; School of Biosciences, University of Sheffield, Sheffield, UK; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Liu Q; Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Beijing, China; Chinese Academy of Sciences, Shanghai Institute of Materia Medica, Beijing, China., Cowieson NP; Harwell Science and Innovation Campus, Diamond Light Source, Didcot, Oxfordshire, UK., Ahel I; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. Electronic address: ivan.ahel@path.ox.ac.uk., Filippov DV; Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands. Electronic address: filippov@lic.leidenuniv.nl., Rack JGM; Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter, Exeter, UK. Electronic address: j.rack@exeter.ac.uk.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Oct; Vol. 300 (10), pp. 107770. Date of Electronic Publication: 2024 Sep 11.
DOI:	10.1016/j.jbc.2024.107770
Abstrakt:	Dynamic ADP-ribosylation signaling is a crucial pathway that controls fundamental cellular processes, in particular, the response to cellular stresses such as DNA damage, reactive oxygen species, and infection. In some pathogenic microbes, the response to oxidative stress is controlled by a SirTM/zinc-containing macrodomain (Zn-Macro) pair responsible for establishment and removal of the modification, respectively. Targeting this defence mechanism against the host's innate immune response may lead to novel approaches to support the fight against emerging antimicrobial resistance. Earlier studies suggested that Zn-Macros play a key role in the activation of this defence. Therefore, we used phylogenetic, biochemical, and structural approaches to elucidate the functional properties of these enzymes. Using the substrate mimetic asparagine-ADP-ribose as well as the ADP-ribose product, we characterize the catalytic role of the zinc ion in the removal of the ADP-ribosyl modification. Furthermore, we determined structural properties that contribute to substrate selectivity within the different Zn-Macro branches. Together, our data not only give new insights into the Zn-Macro family but also highlight their distinct features that may be exploited for the development of future therapies. Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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