Sandbox Reserved 822: Difference between revisions
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== Ligand Interaction == | == Ligand Interaction == | ||
[[Image:1w1h Ins(1,3,4,5)P4 binding.jpg|right|320px|thumb|Fig.2 Ins(1,3,4,5)P<sub>4</sub> binding to the PH domain of PDK1. Interactions of Ins(1,3,4,5)P<sub>4</sub> (marine) with protein residues (green) are shown in a stereo representation. Hydrogen bonds are indicated as black dotted lines. Conserved water molecules are shown as yellow spheres, not conserved water molecules are coloured magenta. <ref name="Structural"> PMID: 524332 </ref>]] | [[Image:1w1h Ins(1,3,4,5)P4 binding.jpg|right|320px|thumb|Fig.2 Ins(1,3,4,5)P<sub>4</sub> binding to the PH domain of PDK1. Interactions of Ins(1,3,4,5)P<sub>4</sub> (marine) with protein residues (green) are shown in a stereo representation. Hydrogen bonds are indicated as black dotted lines. Conserved water molecules are shown as yellow spheres, not conserved water molecules are coloured magenta. <ref name="Structural"> PMID: 524332 </ref>]] | ||
The PH domain of PDK1 binds inositol phosphates and phosphatidylinositol phosphates with different affinities depending on the phosphorylation state of the molecules. These interactions target PDK1 to particular locations inside the cell and are therefore crucial for the flawless execution of signaling pathways in which PDK1 is involved. | The PH domain of PDK1 binds inositol phosphates and phosphatidylinositol phosphates with different affinities depending on the phosphorylation state of the molecules. These interactions target PDK1 to particular locations inside the cell and are therefore crucial for the flawless execution of signaling pathways in which PDK1 is involved.<ref name="Structural" /> | ||
=== Binding site === | === Binding site === | ||
The <scene name='56/568020/Active_site/1'>binding site</scene> is formed by VL 1-3 which create a shallow, positively charged pocket at the open end of the β barrel. The structure was determined from a crystal grown in the presence of Ins(1,3,4,5)P<sub>4</sub>, which is the head group of PtdIns(3,4,5)P<sub>3</sub>. The phosphoinositide-binding site is lined by positively charged residues which contact the phosphates of Ins(1,3,4,5)P<sub>4</sub> by forming up to 11 hydrogen bonds. <scene name='56/568020/Arg472/1'>Arg472</scene> forms two hydrogen bonds to the phosphate in the D1 position (D1-phosphate). <scene name='56/568020/Argandlys/1'>Arg474 and Lys465</scene> contact the D3-phosphate with three hydrogen bonds in total (two for Arg474, one for Lys465). <scene name='56/568020/Lys495/1'>Lys495</scene> is also in close proximity (4.4 Å) of the D3-phosphate and is able to interact with it. <scene name='56/568020/Lys_tyr_and_arg/2'>Lys465, Tyr486 and Arg521</scene> form up to four hydrogen bonds to the D4-phosphate. The D5-phosphate is contacted by <scene name='56/568020/Lys467/1'>Lys467</scene> with one hydrogen bond. The D2- and D6-hydroxy groups show no direct interactions with the protein. | The <scene name='56/568020/Active_site/1'>binding site</scene> is formed by VL 1-3 which create a shallow, positively charged pocket at the open end of the β barrel. The structure was determined from a crystal grown in the presence of Ins(1,3,4,5)P<sub>4</sub>, which is the head group of PtdIns(3,4,5)P<sub>3</sub>. The phosphoinositide-binding site is lined by positively charged residues which contact the phosphates of Ins(1,3,4,5)P<sub>4</sub> by forming up to 11 hydrogen bonds. <scene name='56/568020/Arg472/1'>Arg472</scene> forms two hydrogen bonds to the phosphate in the D1 position (D1-phosphate). <scene name='56/568020/Argandlys/1'>Arg474 and Lys465</scene> contact the D3-phosphate with three hydrogen bonds in total (two for Arg474, one for Lys465). <scene name='56/568020/Lys495/1'>Lys495</scene> is also in close proximity (4.4 Å) of the D3-phosphate and is able to interact with it. <scene name='56/568020/Lys_tyr_and_arg/2'>Lys465, Tyr486 and Arg521</scene> form up to four hydrogen bonds to the D4-phosphate. The D5-phosphate is contacted by <scene name='56/568020/Lys467/1'>Lys467</scene> with one hydrogen bond. The D2- and D6-hydroxy groups show no direct interactions with the protein.<ref name="Structural" /> | ||
