title: Kinetics and thermodynamics of zinc(II) and arsenic(III) binding to XPA and PARP-1 zinc finger peptides.
abstract: 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.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Electronic address: JHuestis100@salud.unm.edu.
authors: Juliana
authors: J
authors: Huestis
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Electronic address: XZhou@salud.unm.edu.
authors: Xixi
authors: X
authors: Zhou
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Electronic address: LChen01@salud.unm.edu.
authors: Li
authors: L
authors: Chen
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Electronic address: CFeng@salud.unm.edu.
authors: Changjian
authors: C
authors: Feng
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Electronic address: LHudson@salud.unm.edu.
authors: Laurie G
authors: LG
authors: Hudson
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Electronic address: KLiu@salud.unm.edu.
authors: Ke Jian
authors: KJ
authors: Liu
mesh_terms: D001151:Arsenic / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013816:Thermodynamics; D051760:Xeroderma Pigmentosum Group A Protein / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D010455:Peptides; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D015032:Zinc; D001151:Arsenic
keywords: Arsenic(III); Kinetics; PARP-1; Thermodynamics; XPA; Zinc(II)