User:Asif Hossain/Sandbox 1: Difference between revisions

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===Additional Features===

There are two potassium ions bound in the HDAC8 structure. Potassium 1 is 7Å away from the active site while potassium 2 lies toward the exterior of the HDAC8.<ref name="Vannini, A., Volpari, C., Filocamo, G.">Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., ... & Steinkühler, C. (2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences, 101(42), 15064-15069. https://dx.doi.org/10.1073%2Fpnas.0404603101</ref>. It is suggested that potassium 1 is of interest to the active site of HDAC8 because it is tethered to the enzyme by the main chain carbonyl oxygens of Asp178 and His180 which stabilizes the Zn<sup>2+</sup> in the active site. Furthermore, the potassium ion increases the positive charge in the active site and this could help stabilize the oxyanion hole that is formed in the transition state.<ref name="Vannini, A., Volpari, C., Filocamo, G.">Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., ... & Steinkühler, C. (2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences, 101(42), 15064-15069. https://dx.doi.org/10.1073%2Fpnas.0404603101</ref>

There are two <scene name='81/811087/Potassium_ion/2'>potassium ions</scene> bound in the HDAC8 structure. Potassium 1 is 7Å away from the active site while potassium 2 lies toward the exterior of the HDAC8.<ref name="Vannini, A., Volpari, C., Filocamo, G.">Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., ... & Steinkühler, C. (2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences, 101(42), 15064-15069. https://dx.doi.org/10.1073%2Fpnas.0404603101</ref>. It is suggested that potassium 1 is of interest to the active site of HDAC8 because it is tethered to the enzyme by the main chain carbonyl oxygens of Asp178 and His180 which stabilizes the Zn<sup>2+</sup> in the active site. Furthermore, the potassium ion increases the positive charge in the active site and this could help stabilize the oxyanion hole that is formed in the transition state.<ref name="Vannini, A., Volpari, C., Filocamo, G.">Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., ... & Steinkühler, C. (2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences, 101(42), 15064-15069. https://dx.doi.org/10.1073%2Fpnas.0404603101</ref>

<scene name='81/811087/Active_site_loop_1_s30-k36/11'>N-Terminus L1 loop </scene>(amino acid residues 30-36) makes up a significant part of the active site pocket. It is suggested that this loop has high flexibility that enables HDAC8 to more efficiently adjust binding to different ligands. <ref name="Somoza">Somoza J, Skene R. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure, 12(7), 1325-1334.2004. https://doi.org/10.1016/j.str.2004.04.012 </ref>

@@ Line 27: / Line 27: @@
 ===Additional Features===
-There are two potassium ions bound in the HDAC8 structure. Potassium 1 is 7Å away from the active site while potassium 2 lies toward the exterior of the HDAC8.<ref name="Vannini, A., Volpari, C., Filocamo, G.">Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., ... & Steinkühler, C. (2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences, 101(42), 15064-15069. https://dx.doi.org/10.1073%2Fpnas.0404603101</ref>. It is suggested that potassium 1 is of interest to the active site of HDAC8 because it is tethered to the enzyme by the main chain carbonyl oxygens of Asp178 and His180 which stabilizes the Zn<sup>2+</sup> in the active site. Furthermore, the potassium ion increases the positive charge in the active site and this could help stabilize the oxyanion hole that is formed in the transition state.<ref name="Vannini, A., Volpari, C., Filocamo, G.">Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., ... & Steinkühler, C. (2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences, 101(42), 15064-15069. https://dx.doi.org/10.1073%2Fpnas.0404603101</ref>
+There are two <scene name='81/811087/Potassium_ion/2'>potassium ions</scene> bound in the HDAC8 structure. Potassium 1 is 7Å away from the active site while potassium 2 lies toward the exterior of the HDAC8.<ref name="Vannini, A., Volpari, C., Filocamo, G.">Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., ... & Steinkühler, C. (2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences, 101(42), 15064-15069. https://dx.doi.org/10.1073%2Fpnas.0404603101</ref>. It is suggested that potassium 1 is of interest to the active site of HDAC8 because it is tethered to the enzyme by the main chain carbonyl oxygens of Asp178 and His180 which stabilizes the Zn<sup>2+</sup> in the active site. Furthermore, the potassium ion increases the positive charge in the active site and this could help stabilize the oxyanion hole that is formed in the transition state.<ref name="Vannini, A., Volpari, C., Filocamo, G.">Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., ... & Steinkühler, C. (2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences, 101(42), 15064-15069. https://dx.doi.org/10.1073%2Fpnas.0404603101</ref>
 <scene name='81/811087/Active_site_loop_1_s30-k36/11'>N-Terminus L1 loop </scene>(amino acid residues 30-36) makes up a significant part of the active site pocket. It is suggested that this loop has high flexibility that enables HDAC8 to more efficiently adjust binding to different ligands. <ref name="Somoza">Somoza J, Skene R. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure, 12(7), 1325-1334.2004. https://doi.org/10.1016/j.str.2004.04.012 </ref>