Sandbox Reserved 1053: Difference between revisions

Many zinc-dependent proteins are transcriptional regulators<ref>DOI: 10.1128/MMBR.00015-06</ref>. Czr A fits into this category as an [https://en.wikipedia.org/wiki/Allosteric_regulation allosteric inhibitor] of the czr operon. Two [https://en.wikipedia.org/wiki/Zinc Zn⁺²] ions may bind to the dimer<ref name="critical"/>, at the location of the <scene name='69/694220/A5_helices__zn_binding/2'>α5 helix</scene> from each monomer. As zinc binds, the α5 helices <scene name='69/694218/2kjc_zinc_bound/1'>unalign</scene> to inhibit the DNA binding residues (Figure 2). Furthermore, CzrA must be in its dimer form for zinc to bind. The <scene name='69/694220/Spacefill_zinc_pockets/1'>zinc binding pockets</scene> are formed by two residues from each monomer, so Zn⁺² cannot bind to the monomer. The <scene name='69/694220/Zinc_binding_residues/7'>zinc binding site</scene> is formed by Asp84 and His 6 from one monomer, as well as His97 and His100 from the other monomer. Zinc ions were not present in the solution NMR structure<ref name="critical"/>, so a representation of a zinc ion in the binding pocket has been drawn in Figure 4.  The large number of histidines used in the Czr A zinc pocket is a repetitive and commonly found feature in zinc-binding proteins <ref>Miller J, McLachlan AD, Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985 Jun 4;4(6):1609-1614.</ref>.

Zn⁺² binding is driven by a large [https://en.wikipedia.org/wiki/Entropy entropic] gain <ref>DOI:10.1021/ja906131b</ref>. Water molecules around the metal ion and Czr A protein are displaced, and gain greater freedom. This gain in entropy allows Zn⁺² to bind to Czr A with reasonable affinity and speed in vivo. The zinc⁺² ion forms a tetrahedral complex with four residues (Figure 4).  Other metal ions that may form a tetrahedral complex will have some affinity for Czr A; however, the metal binding pocket of Czr A has been optimized to bind Zn⁺² with the highest affinity.