Protein glycation by ADP-ribose: Studies of model conjugates

Cervantes-Laurean, Daniel; Minter, David E.; Jacobson, Elaine L.; Jacobson, Myron K.

doi:10.1021/bi00057a017

Cited by 109 publications

(101 citation statements)

References 24 publications

(29 reference statements)

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“…In addition to this signal, the expected signals for the five adenine carbon atoms (δ ; 121.5 ppm, 142.4 ppm, 151.7 ppm, 154.5 ppm and 157.2 ppm) were observed (spectrum not shown). These chromatographic and spectroscopic data were in complete agreement with our previous analysis of the initial ketoamine product formed from the reaction of n-butylamine with ADP-ribose, where detailed "H-NMR analysis established the carbonyl group at position 2hh [29]. Taken together, the chromatographic and spectroscopic data indicate that the early glycation product (P1) is most probably the ketoamine N α -acetyl-N ε -(1hh-deoxy-ADP-ribulos-1hh-yl)--lysine that is converted to epimeric reduction products following treatment with NaBH % (Scheme 1).…”

Section: Structure Elucidation Of the Carbonyl Compound From Early Glsupporting

confidence: 89%

“…The co-ordinated activities of these two enzymes results in the conversion of a large fraction of the millimolar-range NAD pool within minutes to free ADPribose in close proximity to basic histones [22,23]. The possibility that histone carbonylation in i o is the result at least in part of glycation is supported by earlier studies by Hilz and co-workers that described ADP-ribose conjugates of histone H1 in hepatoma cells following alkylating stress [38] with chemical stability similar to histone glycation conjugates [29].…”

Section: Discussionmentioning

confidence: 91%

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Histone carbonylation in vivo and in vitro

Wondrak

Cervantes-Laurean

Jacobson

et al. 2000

Biochemical Journal

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Non-enzymic damage to nuclear proteins has potentially severe consequences for the maintenance of genomic integrity. Introduction of carbonyl groups into histones in vivo and in vitro was assessed by Western blot immunoassay and reductive incorporation of tritium from radiolabelled NaBH4 (sodium borohydride). Histone H1 extracted from bovine thymus, liver and spleen was found to contain significantly elevated amounts of protein-bound carbonyl groups as compared with core histones. The carbonyl content of nuclear proteins of rat pheochromocytoma cells (PC12 cells) was not greatly increased following oxidative stress induced by H2O2, but was significantly increased following alkylating stress induced by N-methyl-N´-nitro-N-nitrosoguanidine or by combined oxidative and alkylating stress. Free ADP-ribose, a reducing sugar generated in the nucleus in proportion to DNA strand breaks, was shown to be a potent histone H1 carbonylating agent in isolated PC12 cell nuclei. Studies of the mechanism of histone H1 modification by ADP-ribose indicate that carbonylation involves formation of a stable acyclic ketoamine. Our results demonstrate preferential histone H1 carbonylation in vivo, with potentially important consequences for chromatin structure and function.

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Section: Structure Elucidation Of the Carbonyl Compound From Early Glsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 91%

Histone carbonylation in vivo and in vitro

Wondrak

Cervantes-Laurean

Jacobson

et al. 2000

Biochemical Journal

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“…5). This chemistry is precedented in ADP-ribose-amine model conjugates (33). Opening of the ribose ring leads to the remarkable shift in metal coordination whereby the substrate moves form coordinating Mn A with OH2Ј and OH3Ј to OH3Ј and the previously ring-bound OH4Ј (Fig.…”

Section: Discussion Catalytic Mechanism Of De-adp-ribosylationmentioning

confidence: 95%

Mechanism of ADP-ribosylation removal revealed by the structure and ligand complexes of the dimanganese mono-ADP-ribosylhydrolase DraG

Berthold

Wang²,

Nordlund³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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ADP-ribosylation is a ubiquitous regulatory posttranslational modification involved in numerous key processes such as DNA repair, transcription, cell differentiation, apoptosis, and the pathogenic mechanism of certain bacterial toxins. Despite the importance of this reversible process, very little is known about the structure and mechanism of the hydrolases that catalyze removal of the ADP-ribose moiety. In the phototrophic bacterium Rhodospirillum rubrum, dinitrogenase reductase-activating glycohydrolase (DraG), a dimanganese enzyme that reversibly associates with the cell membrane, is a key player in the regulation of nitrogenase activity. DraG has long served as a model protein for ADP-ribosylhydrolases. Here, we present the crystal structure of DraG in the holo and ADP-ribose bound forms. We also present the structure of a reaction intermediate analogue and propose a detailed catalytic mechanism for protein de-ADP-ribosylation involving ring opening of the substrate ribose. In addition, the particular manganese coordination in DraG suggests a rationale for the enzyme's preference for manganese over magnesium, although not requiring a redox active metal for the reaction.binuclear dinuclear ͉ bioinorganic chemistry ͉ covalent modification ͉ nitrogen fixation ͉ posttranslational modifications P osttranslational modification of proteins by the attachment of chemical groups is used by cells from all kingdoms of life and occurs in several forms. Through the reversible covalent modification of specific amino acid side chains, enzyme activity, or protein function can be switched on and off as a rapid response to environmental stimuli. ADP-ribosylation is a posttranslational modification existing in two distinct forms, mono-and poly-ADPribosylation, resulting from the attachment of a single ADP-ribose moiety or a polymeric ADP-ribose chain structure, respectively, to the protein (1, 2).Mono-ADP-ribosylation was first discovered as a process used in the action of several bacterial toxins, including cholera-, diphtheria-, and pertussis toxin (3, 4). The pathogenesis of these diseases involves ADP-ribosylation of specific human proteins, catalyzed by the toxins, thereby affecting the activity of the modified proteins. In human physiology, mono-ADP-ribosylation is found in the regulation of cell-cell and cell-matrix interactions, as well as part of immune function (5, 6). Poly-ADP-ribosylation is involved in many fundamental processes such as DNA repair, transcription and cell differentiation, and is also implicated in carcinogenesis (6-8). Poly-ADP-ribosylation inhibitors are currently in phase II clinical trials for treatment of breast and ovarian cancer (9).Mono-ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs) and is specifically targeted to amino acids residues such as Arg, Asn, Glu, Asp, Cys, diphthamide, or phosphoserine. The reaction is stereospecific, using ␤-NAD ϩ as a substrate, forming the ␣-anomer of the ADP-ribosylated amino acid and releasing nicotinamide (10) (Fig. 1). PolyADP-ribosylation i...

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“…Since glycation by glucose is usually a slow reaction (weeks and months), we have investigated glycation with the pentose ri-bose, a more reactive analogue of glucose (40,41). Those studies led to the unique preparation, kinetic characterization, and stabilization of a reactive glycation intermediate in ribonuclease A.…”

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confidence: 99%