Sandbox Reserved 1072: Difference between revisions
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==CZB Domains and Zinc Binding Site== | ==CZB Domains and Zinc Binding Site== | ||
The <scene name='69/694239/Zb_domain_residues_19-90/7'>CZB domains</scene>, residues 19-90, | The <scene name='69/694239/Zb_domain_residues_19-90/7'>CZB domains</scene>, residues 19-90, regulate the function of DgcZ due to the presence of two <scene name='69/694239/Zinc_binding_domain_zmout/2'>allosteric binding sites</scene>, which bind Zinc cooperatively. Four residues bind Zinc with a high affinity even at 10<sup>-16</sup>M concentrations of Zinc in solution. Due to the tightness of Zinc binding, the complete enzyme has not yet been crystallized in its active conformation without the presence of Zinc metal inhibitor. When Zinc is bound, DgcZ activity is limited<sup>[3]</sup>. | ||
[[Image:Zinc binding site labels.jpg|250 px|left|thumb|'''Figure 6: Zn<sup>+2</sup> Coordination to amino acid residues.''' Three of the four 𝝰 helices of the CZB domains of DgcZ coordinate to the Zn<sup>+2</sup> ion for binding.]] | [[Image:Zinc binding site labels.jpg|250 px|left|thumb|'''Figure 6: Zn<sup>+2</sup> Coordination to amino acid residues.''' Three of the four 𝝰 helices of the CZB domains of DgcZ coordinate to the Zn<sup>+2</sup> ion for binding.]] | ||
Most cells possess efficient Zinc uptake systems, as Zinc is a reactive Lewis Acid. Zinc binds incredibly tightly to this enzyme at subfemtomolar concentrations, attributing to why Zinc co-purified with the protein. Zinc allosterically inhibits the activity of enzyme DgcZ through two allosteric binding sites located on the CZB domains <sup>[8]</sup>. The function of the active site of the GGEEF domains are thus inhibited and regulation is prevented. The CZB domains are folded into four anti-parallel α-helices as 2-fold symmetric homodimers, with the N-terminus on helix 𝝰4. The allosteric binding site includes a <scene name='69/694239/Zinc_binding_domain_zm_in/2'>3His/1Cys</scene> motif that uses amino acids H22 of 𝝰1, C52 of 𝝰2, and H79 and H83 of 𝝰3, spanning three of the four alpha helices of each CZB domain and coordinating the Zinc residue in a tetrahedral fashion (Figure 6). For <scene name='69/694239/Ntermctermdgcz/2'>clarification</scene>, the entirety of 𝝰helix 2 on one monomer of CZB is not successfully crystallized after the Cys52 residue and is not the N-terminal residue<sup>[3]</sup>. | Most cells possess efficient Zinc uptake systems, as Zinc is a reactive Lewis Acid. Zinc binds incredibly tightly to this enzyme at subfemtomolar concentrations, attributing to why Zinc co-purified with the protein. Zinc allosterically inhibits the activity of enzyme DgcZ through two allosteric binding sites located on the CZB domains <sup>[8]</sup>. The function of the active site of the GGEEF domains are thus inhibited and regulation is prevented. The CZB domains are folded into four anti-parallel α-helices as 2-fold symmetric homodimers, with the N-terminus on helix 𝝰4. The allosteric binding site includes a <scene name='69/694239/Zinc_binding_domain_zm_in/2'>3His/1Cys</scene> motif that uses amino acids H22 of 𝝰1, C52 of 𝝰2, and H79 and H83 of 𝝰3, spanning three of the four alpha helices of each CZB domain and coordinating the Zinc residue in a tetrahedral fashion (Figure 6). For <scene name='69/694239/Ntermctermdgcz/2'>clarification</scene>, the entirety of 𝝰helix 2 on one monomer of CZB is not successfully crystallized after the Cys52 residue and is not the N-terminal residue<sup>[3]</sup>. | ||
