Sandbox Reserved 1490: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
{{Sandbox_Reserved_ESBS}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | {{Sandbox_Reserved_ESBS}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | ||
== | ==Crystal structure of cytoplasmic kinase domain of Tie2 in complex with decipera compound DP1919== | ||
<StructureSection load='6MWE' size='340' side='right' caption='Caption for this structure' scene='' name='pp'> | <StructureSection load='6MWE' size='340' side='right' caption='Caption for this structure' scene='' name='pp'> | ||
The protein we are focusing one is a protein kinase receptor to a family of ligands called angiopoietins. This receptor is a Tyrosine Kinase TIE2. We are going to analyze the kinase domain of this protein | The protein we are focusing one is a protein kinase receptor to a family of ligands called angiopoietins. This receptor is a Tyrosine Kinase TIE2. We are going to analyze the kinase domain of this protein | ||
| Line 31: | Line 31: | ||
Looking more closely at the TIE2 intracellular domain, 1106 is found at the base of a loop formed between the C-terminus tail and the C-terminus lobe of the kinase. The OH group of Tyr-1106 is thus directly into the solvent and accessible to phosphorylation. However, Tyr-1100 is not solvent exposed : thereby implying that the carboxy-terminal tail must undergo a conformational change upon activation of the receptor to expose this tyrosine residue for phosphorylation.<ref>PMID:12665569</ref> | Looking more closely at the TIE2 intracellular domain, 1106 is found at the base of a loop formed between the C-terminus tail and the C-terminus lobe of the kinase. The OH group of Tyr-1106 is thus directly into the solvent and accessible to phosphorylation. However, Tyr-1100 is not solvent exposed : thereby implying that the carboxy-terminal tail must undergo a conformational change upon activation of the receptor to expose this tyrosine residue for phosphorylation.<ref>PMID:12665569</ref> | ||
Consequent to ANGPT1 stimulation, the SH2 domain-containing p85 subunit of phosphatidylinositol (PI) 3-kinase is recruited to TIE via tyrosine residue 1100 in the C-end tail of the receptor, leading to activation of the enzyme.<ref>PMID:12665569</ref> | Consequent to ANGPT1 stimulation, the SH2 domain-containing p85 subunit of phosphatidylinositol (PI) 3-kinase [[2pna]] is recruited to TIE via tyrosine residue 1100 in the C-end tail of the receptor, leading to activation of the enzyme.<ref>PMID:12665569</ref> | ||
Interestingly, inhibition of PI 3′ kinase activity can only partially inhibit the chemotactic effect of ANGPT1 on endothelial cells, thereby implying that additional TIE2 binding partners may also contribute to ANGPT1-mediated endothelial cell migration. Phosphorylation of TIE2 further results in its association with a docking protein related to downstream of kinase (Dok), known as Dok-R, it allows Dok-R to serve as a substrate of TIE2 and thereby become tyrosine phosphorylated.<ref>PMID:12665569</ref> | Interestingly, inhibition of PI 3′ kinase activity can only partially inhibit the chemotactic effect of ANGPT1 on endothelial cells, thereby implying that additional TIE2 binding partners may also contribute to ANGPT1-mediated endothelial cell migration. Phosphorylation of TIE2 further results in its association with a docking protein related to downstream of kinase (Dok), known as Dok-R, it allows Dok-R to serve as a substrate of TIE2 and thereby become tyrosine phosphorylated.<ref>PMID:12665569</ref> | ||
| Line 57: | Line 57: | ||
====Regions ==== | ====Regions ==== | ||
– Extracellular region : AA 23 to 748 (already found 3D structures | – Extracellular region : AA 23 to 748 (already found 3D structures: [[2gy5]], [[2gy7]], [[4k0v]], [[5mya]], [[5myb]], [[5utk]]) | ||
– Transmembrane region : AA 749 to 769 | – Transmembrane region : AA 749 to 769 | ||
– Cytoplasmic region : AA 770 to 1124 | – Cytoplasmic region : AA 770 to 1124 (already found 3D structures: [[1fvr]], [[2oo8]], [[2osc]], [[2wqb]], [[3bea]], [[3l8p]], [[4x3j]] | ||
====Domains ==== | ====Domains ==== | ||