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Czr A is a transcriptional repressor protein responsible for the regulation of the Czr operon<ref name="critical">Arunkumar A., Campanello G., Giedroc D. (2009). Solution Structure of a | Czr A is a transcriptional repressor protein responsible for the regulation of the Czr operon<ref name="critical">Arunkumar A., Campanello G., Giedroc D. (2009). Solution Structure of a | ||
paradigm ArsR family zinc sensor in the DNA-bound state. PNAS 106:43 | paradigm ArsR family zinc sensor in the DNA-bound state. PNAS 106:43 | ||
18177-18182.</ref>. The Czr operon contains genes for the proteins Czr A and [http://proteopedia.org/wiki/index.php/3byr Czr B]. Czr B is a Zinc transport protein which moves Zn<sup>2+</sup> out of a cell while Czr A regulates this process by controlling expression level of Czr B. When relatively low amounts of zinc are present in the cell Czr A will bind to DNA, preventing the progression of RNA polymerase and thus inhibiting expression of Czr B. Decreased expression of Czr B results in the ability of the cell to retain Zn<sup>2+</sup> more readily. Because Czr A and Czr B are transcribed as part of the same operon, an inhibitor of Czr A must be readily available to allow full transcription of Czr B when necessary. Czr A is noncompetitively inhibited by the binding of two Zn<sup>2+</sup> ions, which is ideal in that this allows for expression of Czr B, a Zn<sup>2+</sup> transporter to be dependent on the relative amount of Zn<sup>2+</sup> in the cell. Czr A displays two different conformations; the first typically binds DNA and has relatively low affinity for Zn<sup>2+</sup>. In this conformation the <scene name='69/694220/A5_helices__dna_binding/1'>a5 helices are aligned</scene>. Binding of zinc drives a conformational change in which the <scene name='69/694220/A5_helices_dna_binding/1'>a5 helices become unaligned</scene>, lowering the affinity for DNA. | 18177-18182.</ref>. The Czr operon contains genes for the proteins Czr A and [http://proteopedia.org/wiki/index.php/3byr Czr B]. Czr B is a Zinc transport protein which moves Zn<sup>2+</sup> out of a cell while Czr A regulates this process by controlling expression level of Czr B. When relatively low amounts of zinc are present in the cell Czr A will bind to DNA, preventing the progression of RNA polymerase and thus inhibiting expression of Czr B. Decreased expression of Czr B results in the ability of the cell to retain Zn<sup>2+</sup> more readily. Because Czr A and Czr B are transcribed as part of the same operon, an inhibitor of Czr A must be readily available to allow full transcription of Czr B when necessary. Czr A is noncompetitively inhibited by the binding of two Zn<sup>2+</sup> ions, which is ideal in that this allows for expression of Czr B, a Zn<sup>2+</sup> transporter to be dependent on the relative amount of Zn<sup>2+</sup> in the cell. Czr A displays two different conformations; the first typically binds DNA and has relatively low affinity for Zn<sup>2+</sup> (PDB code: 2kjb). In this conformation the <scene name='69/694220/A5_helices__dna_binding/1'>a5 helices are aligned</scene>. Binding of zinc drives a conformational change (PDB code: 2kjc) in which the <scene name='69/694220/A5_helices_dna_binding/1'>a5 helices become unaligned</scene>, lowering the affinity for DNA. | ||
===DNA Binding === | ===DNA Binding === | ||
Czr A performs it's primary function when bound to DNA<ref name="critical"/>. Each monomeric subunit of the protein binds DNA individually, coming together once attached to the DNA. While bound, Czr A prevents the transcription of the DNA in the Czr operon, acting as a repressor protein and effectively turning off the operon. As was briefly mentioned above, the Czr operon contains the gene responsible for producing Czr B, a metal transport protein which regulates the concentration of zinc in the cell. So, by extension, Czr A is responsible for retaining Zn<sup>2+</sup> inside the cell by inhibiting the production of the protein responsible for transporting zinc out of the cell. | Czr A performs it's primary function when bound to DNA<ref name="critical"/>. Each monomeric subunit of the protein binds DNA individually, coming together once attached to the DNA. While bound, Czr A prevents the transcription of the DNA in the Czr operon, acting as a repressor protein and effectively turning off the operon. As was briefly mentioned above, the Czr operon contains the gene responsible for producing Czr B, a metal transport protein which regulates the concentration of zinc in the cell. So, by extension, Czr A is responsible for retaining Zn<sup>2+</sup> inside the cell by inhibiting the production of the protein responsible for transporting zinc out of the cell. |