title: Design of a colicin E7 based chimeric zinc-finger nuclease.
abstract: Colicin E7 is a natural bacterial toxin. Its nuclease domain (NColE7) enters the target cell and kills it by digesting the nucleic acids. The HNH-motif as the catalytic centre of NColE7 at the C-terminus requires the positively charged N-terminal loop for the nuclease activity-offering opportunities for allosteric control in a NColE7-based artificial nuclease. Accordingly, four novel zinc finger nucleases were designed by computational methods exploiting the special structural features of NColE7. The constructed models were subjected to MD simulations. The comparison of structural stability and functional aspects showed that these models may function as safely controlled artificial nucleases. This study was complemented by random mutagenesis experiments identifying potentially important residues for NColE7 function outside the catalytic region.
authors: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, Szeged, 6720, Hungary.
authors: Eszter
authors: E
authors: Németh
authors: Gabriella K
authors: GK
authors: Schilli
authors: Gábor
authors: G
authors: Nagy
authors: Christoph
authors: C
authors: Hasenhindl
authors: Béla
authors: B
authors: Gyurcsik
authors: Chris
authors: C
authors: Oostenbrink
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D003087:Colicins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D016335:Zinc Fingers
chemical_list: C508089:ColE7 protein, E coli; D003087:Colicins; D004720:Endonucleases