Zinc finger proteins as potential targets for toxic metal ions: differential effects on structure and function.
Zinc finger structures are frequently found in transcription factors and DNA repair proteins, mediating DNA-protein and protein-protein binding. As low concentrations of transition metal compounds, including those of cadmium, nickel, and cobalt, have been shown to interfere with DNA transcription and repair, several studies have been conducted to elucidate potential interactions of toxic metal ions with zinc-binding protein domains. Various effects have been identified, including the displacement of zinc, e.g., by cadmium or cobalt, the formation of mixed complexes, incomplete coordination of toxic metal ions, as well as the oxidation of cysteine residues within the metal-binding domain. Besides the number of cysteine and/or histidine ligands, unique structural features of the respective protein under investigation determine whether or not zinc finger structures are disrupted by one or more transition metals. As improper folding of zinc finger domains is mostly associated with the loss of correct protein function, disruption of zinc finger structures may result in interference with manifold cellular processes involved in gene expression, growth regulation, and maintenance of the genomic integrity.
Hartwig
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University of Karlsruhe, Institute of Food Chemistry and Toxicology, Germany. Andrea.Hartwig@chemie.uni-karlsruhe.de
D001667:Binding, Competitive; D004247:DNA / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D030321:Denys-Drash Syndrome / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008670:Metals / Q000494:pharmacology* / Q000633:toxicity; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D017510:Protein Folding; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers / Q000187:drug effects*
D008670:Metals; D009363:Neoplasm Proteins; D014157:Transcription Factors; D004247:DNA