کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1315818 1499424 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Kinetics and thermodynamics of zinc(II) and arsenic(III) binding to XPA and PARP-1 zinc finger peptides
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Kinetics and thermodynamics of zinc(II) and arsenic(III) binding to XPA and PARP-1 zinc finger peptides
چکیده انگلیسی


• Poly (ADP-Ribose) Polymerase 1 is abbreviated to PARP-1.
• Xeroderma Pigmentosum Complementation Group A is abbreviated to XPA.
• Similar Kd values are shown for As(III) binding to XPA and PARP-1 zinc finger peptides.
• kfast for As(III) binding to PARP-1 peptide is approx. 4 × faster than to XPA peptide.
• Zn(II) binds faster than As(III) to both XPA and PARP-1 zinc finger peptides.

Inhibition of DNA repair is an established mechanism of arsenic co-carcinogenesis, and may be perpetuated by the binding of As(III) to key zinc finger (zf) DNA repair proteins. Validated molecular targets of As(III) include the first zinc finger domain of Poly (ADP-Ribose) Polymerase 1 (PARP-1), and the zinc finger domain of Xeroderma Pigmentosum Complementation Group A (XPA). In order to gain an understanding of the thermodynamic and kinetic parameters of the interaction of As(III) with these two zinc finger motifs, a fluorescence based approach was used to investigate Zn(II) and As(III) binding to synthetic model peptides corresponding to the zf motif of XPA and first zf motif of PARP-1, referred to in this paper as XPAzf and PARP-1zf-1, respectively. While XPAzf and PARP-1zf-1 display similar relative affinities for As(III), PARP-1zf-1 shows a potential kinetic advantage over XPAzf for As(III) binding, with a rate constant for the fast phase of formation of As(III)-PARP-1zf-1 approximately 4-fold higher than for As(III)-XPAzf. However, the binding of Zn(II) with either peptide proceeds at a faster rate than As(III). Notably, XPAzf demonstrates comparable affinities for binding both metals, while PARP-1zf-1 shows a slightly higher affinity for Zn(II), suggesting that the relative concentrations of Zn(II) and As(III) in a system may significantly influence which species predominates in zinc finger occupancy. These results provide insight into the mechanisms underlying interactions between zinc finger structures and As(III), and highlight the potential utility of zinc supplementation in mitigating adverse effects of As(III) on zinc finger functions in vivo.

As(III) and Zn(II) show comparable binding affinities for Xeroderma Pigmentosum Complementation Group A zinc finger peptide (XPAzf). Zn(II) shows a slightly higher affinity than As(III) for Poly (ADP-Ribose) Polymerase 1 zinc finger peptide (PARP-1zf-1). As(III) shows similar affinities for PARP-1zf-1 and XPAzf, but binds approximately 4 times faster to PARP-1zf-1.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 163, October 2016, Pages 45–52
نویسندگان
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