Sandbox Reserved 1172: Difference between revisions
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=== Key Ligand Interactions === | === Key Ligand Interactions === | ||
[[Image:Ligandpocket2.png|200 px|right|thumb|Figure 2: Surface representation of the LPA<sub>1</sub> receptor in tan interacting with its antagonist, ON7, shown in green and red sticks.]] | [[Image:Ligandpocket2.png|200 px|right|thumb|Figure 2: Surface representation of the LPA<sub>1</sub> receptor in tan interacting with its antagonist, ON7, shown in green and red sticks.]] | ||
Three separate interactions with an antagonist of LPA<sub>1</sub>, ON7, help demonstrate the key interactions that stabilize the binding of the LPA phospholipid to this receptor. At the polar region of the binding pocket, the majority of this region is stabilized by <scene name='72/721543/Arg124gln125/ | Three separate interactions with an antagonist of LPA<sub>1</sub>, ON7, help demonstrate the key interactions that stabilize the binding of the LPA phospholipid to this receptor. At the polar region of the binding pocket, the majority of this region is stabilized by <scene name='72/721543/Arg124gln125/3'>Arg124 and Gln125</scene> forming ionic and polar interactions with the carboxylic acid and the hydroxyl group of ON7.<ref name="regpeps">PMID: 26091040</ref> In addition, interplay between <scene name='72/721543/Lys39_and_glu293/4'>Glu293 and Lys39</scene> causes another stabilizing component of the ON7 antagonist. Glu293 forms polar interactions with Lys39, positioning it in close proximity to to the carboxylic acid of ON7, which then interactions with Lys39 via ionic bonding.<ref name="regpeps">PMID: 26091040</ref> While Lys39 is highly conserved among all six LPA receptors, a His40 residue is present that is specific to the LPA<sub>1</sub> receptor. <scene name='72/721543/His40/1'>His40</scene> forms both ionic and polar interactions with the carboxylic acid of ON7. The protonation of this residue has been found to greatly affect the binding affinity of LPA, and is an important link to tumor growth and survival in acidic environments.<ref name="regpeps">PMID: 26091040</ref> | ||
