ADP ribosylation of rat liver lysine-rich histone in vitro.

Riquelme, Patricio T.; Burzio, Luis O.; Koide, S. S.

doi:10.1016/s0021-9258(17)30177-1

Cited by 160 publications

(15 citation statements)

References 46 publications

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“…This aspect must be integrated in designing the HTS and MoA studies for optimal outcome. For instance, although PARP1 is itself a major acceptor of PAR (poly ADP ribose) chains, other substrates for PARylation include core histones 46,47 . It would have to be ensured that the HTS effort and subsequent MoA studies starts with a homogenous population of enzymes with identical modification status.…”

Section: Figure 3 Auto-catalysing Enzymes (A) Auto Inhibition Of the Enzyme Parp1/2 As A Function Of Self Parylation And The Resultant Timentioning

confidence: 99%

Explicit Treatment of Non‐Michaelis‐Menten and Atypical Kinetics in Early Drug Discovery**

Srinivasan

2020

ChemMedChem

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Biological systems are highly regulated. They are also highly resistant to sudden perturbations enabling them to maintain the dynamic equilibrium essential to sustain life. This robustness is conferred by regulatory mechanisms that influence the activity of enzymes/proteins within their cellular context to adapt to changing environmental conditions. However, the initial rules governing the study of enzyme kinetics were mostly tested and implemented for cytosolic enzyme systems that were easy to isolate and/or recombinantly express. Moreover, these enzymes lacked complex regulatory modalities. Now, with academic labs and pharmaceutical companies turning their attention to more‐complex systems (for instance, multiprotein complexes, oligomeric assemblies, membrane proteins and post‐translationally modified proteins), the initial axioms defined by Michaelis‐Menten (MM) kinetics are rendered inadequate, and the development of a new kind of kinetic analysis to study these systems is required. This review strives to present an overview of enzyme kinetic mechanisms that are atypical and, oftentimes, do not conform to the classical MM kinetics. Further, it presents initial ideas on the design and analysis of experiments in early drug‐discovery for such systems, to enable effective screening and characterisation of small‐molecule inhibitors with desirable physiological outcomes.

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Section: Figure 3 Auto-catalysing Enzymes (A) Auto Inhibition Of the Enzyme Parp1/2 As A Function Of Self Parylation And The Resultant Timentioning

confidence: 99%

Explicit Treatment of Non‐Michaelis‐Menten and Atypical Kinetics in Early Drug Discovery**

Srinivasan

2020

ChemMedChem

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“…We favor the view that the former reaction relates more directly to the actual biological function of the enzyme. Regions of histones subject to ADP-ribosylation have recently been studied in detail by Riquelme et al (1979) and Burzio et al (1979). In addition, Stone et al (1978) have made the interesting observation that, in nuclei, poly(ADP-Rib) polymerase catalyzes a reaction whereby two molecules of histone HI are cross-linked by a single chain of 15 to 16 ADP-Rib units.…”

Section: Discussionmentioning

confidence: 99%

Purification and characterization of the major nonhistone protein acceptor for poly(adenosine diphosphate ribose) in HeLa cell nuclei

Jump¹,

Smulson²

1980

Biochemistry

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“…However, the exact modification sites have never been rigorously demonstrated . Through a series of experiments, it was demonstrated that hydroxylamine-labile ADP-ribose bonds of PARP-1 were of a similar type of caboxyl ester as in mono-ADP-ribosylated histones. − According to a detailed study of the automodification biochemistry, PARP-1 was estimated to bear as many as 15 attachment sites for pADPr polymers . Recently, this carboxyl linkage model has been called into question with studies reporting the identification of lysine residues as predominant acceptors of pADPr on PARP-1 .…”

Section: Introductionmentioning

confidence: 99%

Mapping PARP-1 Auto-ADP-ribosylation Sites by Liquid Chromatography–Tandem Mass Spectrometry

et al. 2013

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We demonstrate a novel method for the identification of poly(ADP-ribose) polymerase-1 (PARP-1) autopoly(ADP-ribosyl)ation sites that is suited to collision induced dissociation (CID) tandem mass spectrometry. By employing phosphodiesterase to remove the majority of the poly(ADP-ribose) (pADPr) modification, we reduce the complexity of tandem mass spectrometric analysis of pADPr-modified tryptic peptides. The simplified ribose-5'-phosphate form of the peptides produce tandem mass spectra by CID that are readily interpreted and enable effective localization of the exact sites of PARP-1-catalyzed poly(ADP-ribosyl)ation. In conjunction with a phosphopeptide-like enrichment strategy that captures the ribose-5'-phosphate peptides, we identified eight novel sites of PARP-1 automodification, confirmed the localization of two sites previously reported, and provided evidence for two additional targeted peptides with ambiguous modification site assignments. Given the simplicity of the approach, the method is readily applicable to analysis of complex samples.

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ADP ribosylation of rat liver lysine-rich histone in vitro.

Cited by 160 publications

References 46 publications

Explicit Treatment of Non‐Michaelis‐Menten and Atypical Kinetics in Early Drug Discovery**

Explicit Treatment of Non‐Michaelis‐Menten and Atypical Kinetics in Early Drug Discovery**

Purification and characterization of the major nonhistone protein acceptor for poly(adenosine diphosphate ribose) in HeLa cell nuclei

Mapping PARP-1 Auto-ADP-ribosylation Sites by Liquid Chromatography–Tandem Mass Spectrometry

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