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<StructureSection load='Z-DNA.pdb' size=' | <StructureSection load='Z-DNA.pdb' size='350' side='right' scene='Z-DNA/Z-dna_new/1' caption=''> | ||
'''Z-DNA''' <scene name='Z-DNA/Z-dna_new/1'>(default scene)</scene> is a form of DNA that has a different structure from the more common <scene name='Sandbox_Z-DNA/Bdna/3'>B-DNA</scene> form.It is a left-handed double helix wherein the sugar-phosphate backbone has a zigzag pattern due to the alternate stacking of bases in [http://proteopedia.org/wiki/index.php/Syn_and_anti_nucleosides anti-conformation and syn conformation]. In Z-DNA only a minor groove is present and the major groove is absent. The residues that allow sequence-specific recognition of Z-DNA are present on the convex outer surface.<ref name = 'Rich'> PMID:12838348</ref> This DNA form is thought to play a role in the regulation of gene expression, DNA processing events and/or genetic instability.<ref name = 'Wang'>PMID:17485386</ref> | '''Z-DNA''' <scene name='Z-DNA/Z-dna_new/1'>(default scene)</scene> is a form of DNA that has a different structure from the more common <scene name='Sandbox_Z-DNA/Bdna/3'>B-DNA</scene> form.It is a left-handed double helix wherein the sugar-phosphate backbone has a zigzag pattern due to the alternate stacking of bases in [http://proteopedia.org/wiki/index.php/Syn_and_anti_nucleosides anti-conformation and syn conformation]. In Z-DNA only a minor groove is present and the major groove is absent. The residues that allow sequence-specific recognition of Z-DNA are present on the convex outer surface.<ref name = 'Rich'> PMID:12838348</ref> This DNA form is thought to play a role in the regulation of gene expression, DNA processing events and/or genetic instability.<ref name = 'Wang'>PMID:17485386</ref> | ||
See also [[Z-DNA model tour]] and [[B-DNA tour]]. | |||
== Structure == | == Structure == | ||
Z-DNA (<scene name='Sandbox_Z-DNA/B-z/7'>B-Z DNA junction</scene>, PDB entry [[2acj]]) can form '' | Z-DNA (<scene name='Sandbox_Z-DNA/B-z/7'>B-Z DNA junction</scene>, PDB entry [[2acj]]) can form ''in vitro'' from B-DNA by raising negative super helical stress or under low salt conditions when deoxycytosine is 5-methylated. The formation of Z-DNA ''in vivo'' is an energy requiring process. It forms behind a RNA polymerase moving through a DNA double helix during transcription and is subsequently stabilized due to the generation of negative supercoils. Z-DNA is the first single crystal X-ray structure of a DNA fragment. It was crystallized as a self complementary DNA hexamer d(CG)<sub>3</sub> by Andrew Wang, Alexander Rich and their co-workers at MIT in 1979. <ref name = 'Rich'>PMID:12838348</ref><ref name ='Wang'>PMID:17485386</ref> | ||
Whenever B-DNA transforms into Z-DNA two <scene name='Sandbox_Z-DNA/B-zjunction/7'>B-Z junctions</scene> form. The crystal structure of these junctions revealed<scene name='Sandbox_Z-DNA/Extruded/12'> two extruded bases</scene>, <scene name='Z-DNA/Extruded/2'>adenine</scene> and <scene name='Z-DNA/Extruded/3'>thymine</scene> at the junction. A crucial finding from this structure is that a right handed DNA can transform to a left handed DNA or vice versa by the disruption and extrusion of a base pair. It has also been suggested that the extruded base pairs at B-Z DNA junction may be sites for DNA modification.<ref>PMID:16237447</ref> | Whenever B-DNA transforms into Z-DNA two <scene name='Sandbox_Z-DNA/B-zjunction/7'>B-Z junctions</scene> form. The crystal structure of these junctions revealed<scene name='Sandbox_Z-DNA/Extruded/12'> two extruded bases</scene>, <scene name='Z-DNA/Extruded/2'>adenine</scene> and <scene name='Z-DNA/Extruded/3'>thymine</scene> at the junction. A crucial finding from this structure is that a right handed DNA can transform to a left handed DNA or vice versa by the disruption and extrusion of a base pair. It has also been suggested that the extruded base pairs at B-Z DNA junction may be sites for DNA modification.<ref>PMID:16237447</ref> | ||
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Z-DNA binding proteins have common structural characteristics. The binding domains of these proteins can substitute one another and thus can act as competitive inhibitors against one another. As explained above, disruption in the Z-DNA binding region of E3L reduces its pathogenicity. All these observations are important pointers towards the biological importance of Z-DNA.<ref name ='Wang'>PMID:17485386</ref> | Z-DNA binding proteins have common structural characteristics. The binding domains of these proteins can substitute one another and thus can act as competitive inhibitors against one another. As explained above, disruption in the Z-DNA binding region of E3L reduces its pathogenicity. All these observations are important pointers towards the biological importance of Z-DNA.<ref name ='Wang'>PMID:17485386</ref> | ||
=== High-resolution crystal structure of Z-DNA in complex with Cr3+ cations <ref>DOI 10.1007/s00775-015-1247-5</ref>=== | |||
Trivalent chromium, a d<sup>3</sup> cation, is poorly taken up by living cells. The Cr<sup>3+</sup> ions are the final product of in vivo Cr<sup>6+</sup> metabolism. However, Cr<sup>3+</sup> in contrast to Cr<sup>6+</sup> can form coordination complexes with macromolecules in the cells. In vitro biochemical experiments have shown that exposure of cells to Cr6+ yields binary (DNA–Cr<sup>3+</sup>) and ternary (DNA–Cr<sup>3+</sup>–ligand) adducts, DNA crosslinks, as well as oxidative DNA lesions. Despite the interest in DNA–Cr<sup>3+</sup> interactions in biological systems, the existing literature provides detailed crystallographic structural data for only two, low-resolution DNA–Cr<sup>3+</sup>:DNA polymerase-β complexes, PDB [[1zqe]] (3.7 Å) ֵand [[1huz]] (2.6 ֵÅ). | |||
Our work is part of our project aimed at characterizing metal-binding properties of left-handed Z-DNA helices. The three Cr3+ cations found in the asymmetric unit of the d(CGCGCG)<sub>2</sub>–Cr<sup>3+</sup> crystal structure do not form direct coordination bonds with either the guanine N/O atoms or the phosphate groups of the Z-DNA. <scene name='69/693575/Cv/6'>Note the alternate conformations</scene> (<span style="color:lime;background-color:black;font-weight:bold;">I, green</span>; <span style="color:orange;background-color:black;font-weight:bold;">II, orange</span>) along the DNA chains. <scene name='69/693575/Cv/7'>Click here to see the animation of this scene</scene>. <font color='darkmagenta'><b>Cr<sup>3+</sup> cations shown as purple spheres</b></font>. Instead, only water-mediated contacts between the nucleic acid and the Cr<sup>3+</sup> cations are observed. The coordination spheres of Cr<sup>3+</sup>(1) and Cr<sup>3+</sup>(2) contain six water molecules each. The Cr<sup>3+</sup>(1) and Cr<sup>3+</sup>(2) ions are bridged by three water molecules from their coordination spheres, one of which (Wat1) is split into two sites. The hydration patterns of Cr<sup>3+</sup>(1) and Cr<sup>3+</sup>(2) are <scene name='69/693575/Cv/8'>irregular and difficult to define</scene> (<font color='red'><b>water molecules are represented by red spheres</b></font>). The Cr<sup>3+</sup>(3) cation has <scene name='69/693575/Cv/9'>distorted square pyramidal geometry</scene>. | |||
We have used Z-DNA crystals to obtain accurate information about the geometrical parameters characterizing the coordination of Cr3+ ions by left-handed Z-DNA. The d(CGCGCG)2–Cr<sup>3+</sup> structure is an excellent illustration of the flexibility of the Z-DNA molecule, visible in the adoption of multiple conformations (by the phosphate groups and the G2 nucleotide), in response to changes in its electrostatic and hydration environment, caused by the introduction of hydrated metal complexes. | |||
</StructureSection> | </StructureSection> | ||
__NOTOC__ | |||
== Movie Depicting ADAR1 binding to Z-DNA == | == Movie Depicting ADAR1 binding to Z-DNA == | ||
< | <html5media height="315" width="560">http://www.youtube.com/embed/tvrWkld8TBY</html5media> | ||
== Comparison of the three helices and helical parameters of DNA == | == Comparison of the three helices and helical parameters of DNA == | ||
''Sources''<ref>http://203.129.231.23/indira/nacc/</ref> | ''Sources''<ref>http://203.129.231.23/indira/nacc/</ref> | ||
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
[[1woe]], [[3qba]] – ZDNA hexamer CGCGCG<br /> | [[1woe]], [[3qba]], [[1i0t]], [[6aqt]], [[6aqv]], [[6aqw]], [[6aqx]], [[2ie1]], [[1da1]], [[1ick]], [[313d]], [[314d]], [[390d]], [[391d]], [[392d]], [[3p4j]], [[3qba]], [[3wbo]], [[400d]], [[4fs5]], [[4fs6]], [[4hif]], [[4hig]], [[2hto]], [[2htt]], [[4r15]], [[4xsn]], [[6bst]] – ZDNA hexamer CGCGCG<br /> | ||
[[1v9g]] – ZDNA hexamer CGCGCG - Neutron<br /> | |||
[[1tne]] – ZDNA hexamer CGCGCG - NMR<br /> | |||
[[2obz]] – ZDNA hexamer CGCGUG<br /> | |||
[[362d]] – ZDNA hexamer TGCGCA<br /> | |||
[[1qbj]] – ZDNA hexamer CGCGCG + hADAR1 Zα domain - human<br /> | [[1qbj]] – ZDNA hexamer CGCGCG + hADAR1 Zα domain - human<br /> | ||
[[2heo]] - ZDNA hexamer CGCGCG + Z-DNA-binding protein Zα domain – mouse<br /> | [[2heo]] - ZDNA hexamer CGCGCG + Z-DNA-binding protein Zα domain – mouse<br /> | ||
[[ | [[1sfu]] - ZDNA hexamer CGCGCG + Pox virus Z-DNA-binding protein Zα domain <br /> | ||
[[4wcg]] - ZDNA hexamer CGCGCG + Herpes virus 3 Z-DNA-binding protein Zα domain <br /> | |||
[[1j75]] - ZDNA hexamer CGCGCG + DLM-1 Z-DNA-binding protein Zα domain <br /> | |||
[[3f21]] - ZDNA hexamer CACGTG + double-stranded RNA-specific adenosine deaminase Z-DNA-binding protein Zα domain <br /> | |||
[[3f21]] - ZDNA hexamer CGTACG + double-stranded RNA-specific adenosine deaminase Z-DNA-binding protein Zα domain <br /> | |||
[[3eyi]] - ZDNA hexamer CGCGCG + Z-DNA-binding protein Zβ domain<br /> | |||
[[1j75]] - ZDNA hexamer CGCGCG + DLM-1 Zα domain<br /> | [[1j75]] - ZDNA hexamer CGCGCG + DLM-1 Zα domain<br /> | ||
[[3fqb]] - ZDNA hexamer CGCGTG + Ba<br /> | |||
==Additional Resources== | ==Additional Resources== | ||