Unusual Zn(II) Affinities of Zinc Fingers of Poly(ADP-ribose)Polymerase 1 (PARP-1) Nuclear Protein.

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Bossak K, Goch W, Piatek K, Fraczyk T, Poznanski J, Bonna A, Keil C, Hartwig A, Bal W

Unusual Zn(II) Affinities of Zinc Fingers of Poly(ADP-ribose)Polymerase 1 (PARP-1) Nuclear Protein.

Chem Res Toxicol. 2015 Feb 16;28(2):191-201.

PubMed ID

25549802 [ View in PubMed

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Abstract

Poly(ADP-ribose) polymerase 1 (PARP-1) is a key eukaryotic enzyme,catalyzing the NAD+ dependent poly(ADP-ribosyl)ation of protein substrates, crucial for major DNA repair pathways, and involved in other fundamental cellular processes, such as transcription, cell cycle control, and apoptosis. Its ability to bind DNA depends on two CCHC zinc finger domains, in short, PARPzf1 and PARPzf2. Using spectroscopic methods and competitive titrations with Zn(II), Co(II), and Ni(II) ions, we determined conditional dissociation constants for Zn(II) complexes of PARPzf1 and PARPzf2 at pH 7.4 (HEPESbuffer) as 26 +/- 4 nM and 4 +/- 1 pM, respectively. The former value indicates an extremely low affinity of PARPzf1 toward metal ions, meaning that under cellular conditions PARP1zf might be largely present in a "metal-free" state. This finding provides a clue to the high susceptibility of PARP-1 to oxidative stress but also raises questions regarding the activation of PARPzf1 under cellular conditions. We also determined conditional dissociation constants for Ni(II) complexes of PARPzf1 and PARPzf2 under the same conditions as 0.78 +/- 0.04 muM and 0.26 +/- 0.05 nM, respectively.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Zinc	Poly [ADP-ribose] polymerase 1	Protein	Humans	Unknown	Not Available	Details
Zinc acetate	Poly [ADP-ribose] polymerase 1	Protein	Humans	Unknown	Not Available	Details
Zinc chloride	Poly [ADP-ribose] polymerase 1	Protein	Humans	Unknown	Component of	Details
Zinc sulfate, unspecified form	Poly [ADP-ribose] polymerase 1	Protein	Humans	Unknown	Component of	Details