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ADP-ribosylation of arginine.

Laing S, Unger M, Koch-Nolte F, Haag F - Amino Acids (2010)

Bottom Line: In case of the nucleotide-gated P2X7 ion channel, ADP-ribosylation at R125 in the vicinity of the ligand-binding site causes channel gating.In some cases, ADP-ribosylarginine is processed into secondary posttranslational modifications, e.g. phosphoribosylarginine or ornithine.This review summarizes current knowledge on arginine-specific ADP-ribosylation, focussing on the methods available for its detection, its biological consequences, and the enzymes responsible for this modification and its reversal, and discusses future perspectives for research in this field.

View Article: PubMed Central - PubMed

Affiliation: Campus Forschung, 2. OG Rm 02.0058, Institute of Immunology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

ABSTRACT
Arginine adenosine-5'-diphosphoribosylation (ADP-ribosylation) is an enzyme-catalyzed, potentially reversible posttranslational modification, in which the ADP-ribose moiety is transferred from NAD(+) to the guanidino moiety of arginine. At 540 Da, ADP-ribose has the size of approximately five amino acid residues. In contrast to arginine, which, at neutral pH, is positively charged, ADP-ribose carries two negatively charged phosphate moieties. Arginine ADP-ribosylation, thus, causes a notable change in size and chemical property at the ADP-ribosylation site of the target protein. Often, this causes steric interference of the interaction of the target protein with binding partners, e.g. toxin-catalyzed ADP-ribosylation of actin at R177 sterically blocks actin polymerization. In case of the nucleotide-gated P2X7 ion channel, ADP-ribosylation at R125 in the vicinity of the ligand-binding site causes channel gating. Arginine-specific ADP-ribosyltransferases (ARTs) carry a characteristic R-S-EXE motif that distinguishes these enzymes from structurally related enzymes which catalyze ADP-ribosylation of other amino acid side chains, DNA, or small molecules. Arginine-specific ADP-ribosylation can be inhibited by small molecule arginine analogues such as agmatine or meta-iodobenzylguanidine (MIBG), which themselves can serve as targets for arginine-specific ARTs. ADP-ribosylarginine specific hydrolases (ARHs) can restore target protein function by hydrolytic removal of the entire ADP-ribose moiety. In some cases, ADP-ribosylarginine is processed into secondary posttranslational modifications, e.g. phosphoribosylarginine or ornithine. This review summarizes current knowledge on arginine-specific ADP-ribosylation, focussing on the methods available for its detection, its biological consequences, and the enzymes responsible for this modification and its reversal, and discusses future perspectives for research in this field.

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Schematic diagram of the enzyme catalyzed, reversible posttranslational modification of arginine by ADP-ribose. In the active centre of an ADP-ribosyltransferase (ART), NAD+ is brought into an extended conformation that permits the attack of the target arginine on the β-N-glycosidic bond between nicotinamide and the C1′-atom of the ribose group. This leads to the formation of ADP-ribosylarginine with C1′ in α-conformation, while nicotinamide is released. The native arginine can be recovered by the reverse reaction, catalyzed by an ADP-ribosylarginine hydrolase (ARH). This enzyme hydrolyses the α-glycosidic bond, releasing ADP-ribose
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Fig1: Schematic diagram of the enzyme catalyzed, reversible posttranslational modification of arginine by ADP-ribose. In the active centre of an ADP-ribosyltransferase (ART), NAD+ is brought into an extended conformation that permits the attack of the target arginine on the β-N-glycosidic bond between nicotinamide and the C1′-atom of the ribose group. This leads to the formation of ADP-ribosylarginine with C1′ in α-conformation, while nicotinamide is released. The native arginine can be recovered by the reverse reaction, catalyzed by an ADP-ribosylarginine hydrolase (ARH). This enzyme hydrolyses the α-glycosidic bond, releasing ADP-ribose

Mentions: ADP-ribosylation of arginine is a reversible posttranslational modification (PTM) of proteins in which the ADP-ribose moiety is transferred from NAD+ to the guanidino group of arginine under release of nicotinamide (Fig. 1). This reaction is catalyzed by a subfamily of ADP-ribosyltransferases (ARTs) that bind NAD+ in an extended conformation, enabling the nucleophilic attack of one of the two terminal nitrogen atoms of the guanidino group of arginine on the β-N-glycosidic bond between nicotinamide and the C1′-atom of the ribose-group (Haag and Koch-Nolte 1997; Jacobson and Jacobson 1989; Margarit et al. 2006; Moss and Vaughan 1990; Tsuge et al. 2008). Nicotinamide is released and a new N-glycosidic bond between arginine and ADP-ribose is generated with an inversion of the conformation at the C1′ atom of ADP-ribose from beta to alpha (Fig. 1). Arginine ADP-ribosylation can be fully reversed by specific enzymes (ADP-ribosylhydrolases). Other acceptor amino acids, such as diphthamide (a modified histidine), cysteine or asparagine, are targeted by other sub-families of ADP-ribosyltransferases via a similar reaction mechanism (Berti et al. 1997; Hottiger et al. 2010; Koch-Nolte et al. 2008; Lang et al. 2010; Locht and Antoine 1995).Fig. 1


ADP-ribosylation of arginine.

Laing S, Unger M, Koch-Nolte F, Haag F - Amino Acids (2010)

Schematic diagram of the enzyme catalyzed, reversible posttranslational modification of arginine by ADP-ribose. In the active centre of an ADP-ribosyltransferase (ART), NAD+ is brought into an extended conformation that permits the attack of the target arginine on the β-N-glycosidic bond between nicotinamide and the C1′-atom of the ribose group. This leads to the formation of ADP-ribosylarginine with C1′ in α-conformation, while nicotinamide is released. The native arginine can be recovered by the reverse reaction, catalyzed by an ADP-ribosylarginine hydrolase (ARH). This enzyme hydrolyses the α-glycosidic bond, releasing ADP-ribose
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102197&req=5

Fig1: Schematic diagram of the enzyme catalyzed, reversible posttranslational modification of arginine by ADP-ribose. In the active centre of an ADP-ribosyltransferase (ART), NAD+ is brought into an extended conformation that permits the attack of the target arginine on the β-N-glycosidic bond between nicotinamide and the C1′-atom of the ribose group. This leads to the formation of ADP-ribosylarginine with C1′ in α-conformation, while nicotinamide is released. The native arginine can be recovered by the reverse reaction, catalyzed by an ADP-ribosylarginine hydrolase (ARH). This enzyme hydrolyses the α-glycosidic bond, releasing ADP-ribose
Mentions: ADP-ribosylation of arginine is a reversible posttranslational modification (PTM) of proteins in which the ADP-ribose moiety is transferred from NAD+ to the guanidino group of arginine under release of nicotinamide (Fig. 1). This reaction is catalyzed by a subfamily of ADP-ribosyltransferases (ARTs) that bind NAD+ in an extended conformation, enabling the nucleophilic attack of one of the two terminal nitrogen atoms of the guanidino group of arginine on the β-N-glycosidic bond between nicotinamide and the C1′-atom of the ribose-group (Haag and Koch-Nolte 1997; Jacobson and Jacobson 1989; Margarit et al. 2006; Moss and Vaughan 1990; Tsuge et al. 2008). Nicotinamide is released and a new N-glycosidic bond between arginine and ADP-ribose is generated with an inversion of the conformation at the C1′ atom of ADP-ribose from beta to alpha (Fig. 1). Arginine ADP-ribosylation can be fully reversed by specific enzymes (ADP-ribosylhydrolases). Other acceptor amino acids, such as diphthamide (a modified histidine), cysteine or asparagine, are targeted by other sub-families of ADP-ribosyltransferases via a similar reaction mechanism (Berti et al. 1997; Hottiger et al. 2010; Koch-Nolte et al. 2008; Lang et al. 2010; Locht and Antoine 1995).Fig. 1

Bottom Line: In case of the nucleotide-gated P2X7 ion channel, ADP-ribosylation at R125 in the vicinity of the ligand-binding site causes channel gating.In some cases, ADP-ribosylarginine is processed into secondary posttranslational modifications, e.g. phosphoribosylarginine or ornithine.This review summarizes current knowledge on arginine-specific ADP-ribosylation, focussing on the methods available for its detection, its biological consequences, and the enzymes responsible for this modification and its reversal, and discusses future perspectives for research in this field.

View Article: PubMed Central - PubMed

Affiliation: Campus Forschung, 2. OG Rm 02.0058, Institute of Immunology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

ABSTRACT
Arginine adenosine-5'-diphosphoribosylation (ADP-ribosylation) is an enzyme-catalyzed, potentially reversible posttranslational modification, in which the ADP-ribose moiety is transferred from NAD(+) to the guanidino moiety of arginine. At 540 Da, ADP-ribose has the size of approximately five amino acid residues. In contrast to arginine, which, at neutral pH, is positively charged, ADP-ribose carries two negatively charged phosphate moieties. Arginine ADP-ribosylation, thus, causes a notable change in size and chemical property at the ADP-ribosylation site of the target protein. Often, this causes steric interference of the interaction of the target protein with binding partners, e.g. toxin-catalyzed ADP-ribosylation of actin at R177 sterically blocks actin polymerization. In case of the nucleotide-gated P2X7 ion channel, ADP-ribosylation at R125 in the vicinity of the ligand-binding site causes channel gating. Arginine-specific ADP-ribosyltransferases (ARTs) carry a characteristic R-S-EXE motif that distinguishes these enzymes from structurally related enzymes which catalyze ADP-ribosylation of other amino acid side chains, DNA, or small molecules. Arginine-specific ADP-ribosylation can be inhibited by small molecule arginine analogues such as agmatine or meta-iodobenzylguanidine (MIBG), which themselves can serve as targets for arginine-specific ARTs. ADP-ribosylarginine specific hydrolases (ARHs) can restore target protein function by hydrolytic removal of the entire ADP-ribose moiety. In some cases, ADP-ribosylarginine is processed into secondary posttranslational modifications, e.g. phosphoribosylarginine or ornithine. This review summarizes current knowledge on arginine-specific ADP-ribosylation, focussing on the methods available for its detection, its biological consequences, and the enzymes responsible for this modification and its reversal, and discusses future perspectives for research in this field.

Show MeSH
Related in: MedlinePlus