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User:Asif Hossain/Sandbox 1: Difference between revisions

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<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>
<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>


The activity of HDAC8 is regulated by phosphorylation at <scene name='81/811087/Active_site_loop_1_s30-k36/12'>Ser39</scene> by [https://en.wikipedia.org/wiki/Protein_kinase_A protein kinase A (PKA)] as the phosphorylation has been shown to decrease the enzyme’s activity.<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> It is suggested that the phosphorylation of Ser39 can interfere with the interaction between HDAC8 and the target histone because Ser39 is at the periphery of HDAC8, approximately 20Å from the active site. The interaction is disrupted because the phosphorylated Ser39 elicits a structural rearrangement that reaches the active site and disrupts enzyme activity. Ser39 elicits the rearrangement by interactions with structural elements in the conformational active loop L1, such as Lys36. Therefore, the Ser39 phosphorylation by PKA is likely inducing a conformational change of the L1 loop that prohibits a substrate binding.<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>
The activity of HDAC8 is regulated by phosphorylation at <scene name='81/811087/Active_site_loop_1_s30-k36/12'>Ser39</scene> by [https://en.wikipedia.org/wiki/Protein_kinase_A protein kinase A (PKA)] as the phosphorylation has been shown to decrease the activity of HDAC8.<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> It is suggested that the phosphorylation of Ser39 can interfere with the interaction between HDAC8 and the target histone because Ser39 is at the periphery of HDAC8, approximately 20Å from the active site. The interaction is disrupted because the phosphorylated Ser39 elicits a structural rearrangement that reaches the active site and disrupts enzyme activity. Ser39 elicits the rearrangement by interactions with structural elements in the conformational active loop L1, such as Lys36. Therefore, the Ser39 phosphorylation by PKA is likely inducing a conformational change of the L1 loop that prohibits a substrate binding.<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>




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