@article {46408,
	title = {Structural basis of the metal specificity for nickel regulatory protein NikR.},
	journal = {Biochemistry},
	volume = {47},
	year = {2008},
	month = {2008 Feb 19},
	pages = {1938-46},
	abstract = {<p>In the presence of excess nickel, Escherichia coli NikR regulates cellular nickel uptake by suppressing the transcription of the nik operon, which encodes the nickel uptake transporter, NikABCDE. Previously published in vitro studies have shown that NikR is capable of binding a range of divalent transition metal ions in addition to Ni2+, including Co2+, Cu2+, Zn2+, and Cd2+. To understand how the high-affinity nickel binding site of NikR is able to accommodate these other metal ions, and to improve our understanding of NikR{\textquoteright}s mechanism of binding to DNA, we have determined structures of the metal-binding domain (MBD) of NikR in the apo form and in complex with Cu2+ and Zn2+ ions and compared them with the previously published structures with Ni2+. We observe that Cu2+ ions bind in a manner very similar to that of Ni2+, with a square planar geometry but with longer bond lengths. Crystals grown in the presence of Zn2+ reveal a protein structure similar to that of apo MBD with a disordered alpha3 helix, but with two electron density peaks near the Ni2+ binding site corresponding to two Zn2+ ions. These structural findings along with biochemical data on NikR support a hypothesis that ordering of the alpha3 helix is important for repressor activation.</p>
},
	keywords = {Binding Sites, Circular Dichroism, Escherichia coli Proteins, Metals, Models, Molecular, Protein Conformation, Repressor Proteins},
	issn = {0006-2960},
	doi = {10.1021/bi702006h},
	author = {Phillips, Christine M and Schreiter, Eric R and Guo, Yayi and Wang, Sheila C and Zamble, Deborah B and Drennan, Catherine L}
}
@article {46401,
	title = {NikR-operator complex structure and the mechanism of repressor activation by metal ions.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {103},
	year = {2006},
	month = {2006 Sep 12},
	pages = {13676-81},
	abstract = {<p>Metal ion homeostasis is critical to the survival of all cells. Regulation of nickel concentrations in Escherichia coli is mediated by the NikR repressor via nickel-induced transcriptional repression of the nickel ABC-type transporter, NikABCDE. Here, we report two crystal structures of nickel-activated E. coli NikR, the isolated repressor at 2.1 A resolution and in a complex with its operator DNA sequence from the nik promoter at 3.1 A resolution. Along with the previously published structure of apo-NikR, these structures allow us to evaluate functional proposals for how metal ions activate NikR, delineate the drastic conformational changes required for operator recognition, and describe the formation of a second metal-binding site in the presence of DNA. They also provide a rare set of structural views of a ligand-responsive transcription factor in the unbound, ligand-induced, and DNA-bound states, establishing a model system for the study of ligand-mediated effects on transcription factor function.</p>
},
	keywords = {Amino Acid Sequence, Base Sequence, Binding Sites, Crystallography, Escherichia coli Proteins, Molecular Sequence Data, Nickel, Operator Regions, Genetic, Protein Conformation, Repressor Proteins},
	issn = {0027-8424},
	doi = {10.1073/pnas.0606247103},
	author = {Schreiter, Eric R and Wang, Sheila C and Zamble, Deborah B and Drennan, Catherine L}
}
