Z-DNA: Difference between revisions

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ADAR1 <scene name='Sandbox_Z-DNA/Adar1/3'>(default scene)</scene> belongs to the family of deaminases that modify double stranded mRNA by catalyzing the conversion of adenine to inosine which is then translated to guanosine. It is a complex protein with two Z-DNA binding motifs called <scene name='Sandbox_Z-DNA/Adar1zalpha/10'>Z-alpha</scene> and Z-beta.<ref name = 'Wang'>PMID:17485386</ref> ADAR1 also has three copies of double-stranded RNA binding motif (DRBM) and a catalytic domain related to ''E.coli''  cytidine deaminase.  The binding motif Z-alpha belongs to winged-helix-turn-helix family of proteins. It consists of a <scene name='Z-DNA/Adar1zalpha/1'>helix-turn-helix motif</scene> which has two alpha helices (<scene name='Z-DNA/Adar1zalpha/2'>alpha-2</scene> and <scene name='Z-DNA/Adar1zalpha/3'>alpha-3 also called the recognition</scene>) connected by a short strand of amino acids and a <scene name='Sandbox_Z-DNA/Adar1zalpha/15'>C- terminal beta-sheet</scene>. The beta sheet constrains the fold by contacting the residues between alpha-2 and alpha-3.  
ADAR1 <scene name='Sandbox_Z-DNA/Adar1/3'>(default scene)</scene> belongs to the family of deaminases that modify double stranded mRNA by catalyzing the conversion of adenine to inosine which is then translated to guanosine. It is a complex protein with two Z-DNA binding motifs called <scene name='Sandbox_Z-DNA/Adar1zalpha/10'>Z-alpha</scene> and Z-beta.<ref name = 'Wang'>PMID:17485386</ref> ADAR1 also has three copies of double-stranded RNA binding motif (DRBM) and a catalytic domain related to ''E.coli''  cytidine deaminase.  The binding motif Z-alpha belongs to winged-helix-turn-helix family of proteins. It consists of a <scene name='Z-DNA/Adar1zalpha/1'>helix-turn-helix motif</scene> which has two alpha helices (<scene name='Z-DNA/Adar1zalpha/2'>alpha-2</scene> and <scene name='Z-DNA/Adar1zalpha/3'>alpha-3 also called the recognition</scene>) connected by a short strand of amino acids and a <scene name='Sandbox_Z-DNA/Adar1zalpha/15'>C- terminal beta-sheet</scene>. The beta sheet constrains the fold by contacting the residues between alpha-2 and alpha-3.  


The contact surface between <scene name='Sandbox_Z-DNA/Adar1/4'>Z-alpha and DNA</scene> consists of residues from the helix alpha-3 and COOH-terminal beta hairpin. Hydrogen bonding is present between <scene name='Z-DNA/Aminoacid/1'>amino acids</scene> Lys<sup>169</sup>, Lys <sup>170</sup>, Asn<sup>173</sup>, Arg<sup>174</sup> and Tyr<sup>177</sup> in the helix alpha-3 and <scene name='Z-DNA/Dnanucleotides/1'>five consecutive phosphates on Z-DNA</scene>. Lys<sup>169</sup>, Asn<sup>173</sup>, Arg<sup>174</sup>, Trp<sup>195</sup> make water mediated phosphate contacts with Z-DNA. In addition Thr<sup>191</sup> and Arg<sup>174</sup>  <scene name='Sandbox_Z-DNA/Thrarg/1'> bind to the furanose oxygens </scene> of G2 and G6 on Z-DNA. An important interaction is the <scene name='Sandbox_Z-DNA/Tyrosine_and_g4/1'> Vanderwaal's bond </scene> between aromatic ring of Tyr<sup>177</sup> and the carbon 8 of G4. This is unique to Z-DNA as the interaction requires the base to be in syn conformation. Pro<sup>192</sup>, Pro <sup>193</sup> form another set of  <scene name='Sandbox_Z-DNA/Pro/1'>important Vanderwaal's interactions</scene> with Z-DNA where the pyrrolidine rings bond with the sugar-phosphate backbone from phosphate 2  to phosphate 3. Pro<sup>192</sup>  is conserved in Z-alpha and its homologues and forms a cis peptide bond which positions beta loop against the Z-DNA surface. <ref name = SchwartzRich>PMID: 10364558</ref>  
The contact surface between <scene name='Sandbox_Z-DNA/Adar1/4'>Z-alpha and DNA</scene> consists of residues from the helix alpha-3 and COOH-terminal beta hairpin. Hydrogen bonding is present between <scene name='Z-DNA/Aminoacid/1'>amino acids</scene> Lys<sup>169</sup>, Lys <sup>170</sup>, Asn<sup>173</sup>, Arg<sup>174</sup> and Tyr<sup>177</sup> in the helix alpha-3 and <scene name='Z-DNA/Dnanucleotides/2'>five consecutive phosphates on Z-DNA</scene>. Lys<sup>169</sup>, Asn<sup>173</sup>, Arg<sup>174</sup>, Trp<sup>195</sup> make water mediated phosphate contacts with Z-DNA. In addition Thr<sup>191</sup> and Arg<sup>174</sup>  <scene name='Sandbox_Z-DNA/Thrarg/1'> bind to the furanose oxygens </scene> of G2 and G6 on Z-DNA. An important interaction is the <scene name='Sandbox_Z-DNA/Tyrosine_and_g4/1'> Vanderwaal's bond </scene> between aromatic ring of Tyr<sup>177</sup> and the carbon 8 of G4. This is unique to Z-DNA as the interaction requires the base to be in syn conformation. Pro<sup>192</sup>, Pro <sup>193</sup> form another set of  <scene name='Sandbox_Z-DNA/Pro/1'>important Vanderwaal's interactions</scene> with Z-DNA where the pyrrolidine rings bond with the sugar-phosphate backbone from phosphate 2  to phosphate 3. Pro<sup>192</sup>  is conserved in Z-alpha and its homologues and forms a cis peptide bond which positions beta loop against the Z-DNA surface. <ref name = SchwartzRich>PMID: 10364558</ref>  
[[Image:Hbonding_Z-DNA.png|left|thumb|400px|Polar Interactions between ADAR1 and Z-DNA]]
[[Image:Hbonding_Z-DNA.png|left|thumb|400px|Polar Interactions between ADAR1 and Z-DNA]]


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Adithya Sagar, Eran Hodis, Donald Voet, Karl Oberholser, David Canner, Michal Harel, Alexander Berchansky, Jaime Prilusky, Joel L. Sussman