ArticleThe Journal of biological chemistry2011
Orphan macrodomain protein (human C6orf130) is an O-acyl-ADP-ribose deacylase: solution structure and catalytic properties.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- The Expanding Landscape of ADP-Ribosylation: Protein, DNA, RNA, and Mitochondrial Regulation.Chemical research in toxicology · 2026Review
- Filament formation and NAD processing by noncanonical human FAM118 sirtuins.Nature structural & molecular biology · 2025Article
- The Sirt3-CD38 axis induces mitochondrial dysfunction in hypertrophied heart by regulating mitochondrial calcium overload.European journal of medical research · 2025Article
- MacroD1 sustains mitochondrial integrity and oxidative metabolism.Nature communications · 2025Article
- Half a Century of Progress: The Evolution of Wheat Germ-Based In Vitro Translation into a Versatile Protein Production Method.International journal of molecular sciences · 2025Review
- Insights into mechanisms of ubiquitin ADP-ribosylation reversal.Biochemical Society transactions · 2024Review
- Mono-ADP-Ribosylation of Peptides: An Overview of Synthetic and Chemoenzymatic Methodologies.Chembiochem : a European journal of chemical biology · 2024Review
- ADP-ribose hydrolases: biological functions and potential therapeutic targets.Expert reviews in molecular medicine · 2024Review
- Alzheimer's disease as a causal risk factor for diabetic retinopathy: a Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Review
- Beyond protein modification: the rise of non-canonical ADP-ribosylation.The Biochemical journal · 2022Article
- Article
- TARG1 protects against toxic DNA ADP-ribosylation.Nucleic acids research · 2021Article
- MacroGreen, a simple tool for detection of ADP-ribosylated proteins.Communications biology · 2021Article
- Article
- ADP-ribosylation of RNA and DNA: from in vitro characterization to in vivo function.Nucleic acids research · 2021Review
- ADP-ribosylation systems in bacteria and viruses.Computational and structural biotechnology journal · 2021Review
- Identification of Uncharacterized Components of Prokaryotic Immune Systems and Their Diverse Eukaryotic Reformulations.Journal of bacteriology · 2020Article
- Article
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Post-translational modification of proteins/histones by lysine acylation has profound effects on the physiological function of modified proteins. Deacylation by NAD(+)-dependent sirtuin reactions yields as a product O-acyl-ADP-ribose, which has been implicated as a signaling molecule in modulating cellular processes. Macrodomain-containing proteins are reported to bind NAD(+)-derived metabolites. Here, we describe the structure and function of an orphan macrodomain protein, human C6orf130. This unique 17-kDa protein is a stand-alone macrodomain protein that occupies a distinct branch in the phylogenic tree. We demonstrate that C6orf130 catalyzes the efficient deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose, and O-butyryl-ADP-ribose to produce ADP-ribose (ADPr) and acetate, propionate, and butyrate, respectively. Using NMR spectroscopy, we solved the structure of C6orf130 in the presence and absence of ADPr. The structures showed a canonical fold with a deep ligand (ADPr)-binding cleft. Structural comparisons of apo-C6orf130 and the ADPr-C6orf130 complex revealed fluctuations of the β(5)-α(4) loop that covers the bound ADPr, suggesting that the β(5)-α(4) loop functions as a gate to sequester substrate and offer flexibility to accommodate alternative substrates. The ADPr-C6orf130 complex identified amino acid residues involved in substrate binding and suggested residues that function in catalysis. Site-specific mutagenesis and steady-state kinetic analyses revealed two critical catalytic residues, Ser-35 and Asp-125. We propose a catalytic mechanism for deacylation of O-acyl-ADP-ribose by C6orf130 and discuss the biological implications in the context of reversible protein acylation at lysine residues.
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Registered trials
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