User:Daniel Schemenauer/Sandbox 1: Difference between revisions
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<scene name='72/726404/Scene_7/2'>Mavoglurant</scene> binds within the core of the seven trans-membrane α-helices, forming multiple interactions with the protein that further stabilize the inactive conformation. | <scene name='72/726404/Scene_7/2'>Mavoglurant</scene> binds within the core of the seven trans-membrane α-helices, forming multiple interactions with the protein that further stabilize the inactive conformation. | ||
The bicyclic ring system of the drug is surrounded by a pocket of mainly hydrophobic residues including Val 806, Met 802, Phe 788, Trp 785, Leu 744, Ile 651, Pro 655 and Asn 747<ref name="Primary">PMID: 25042998 </ref> (Figure 1). The carbamate tail of mavoglurant forms a hydrogen bond through its carbonyl oxygen to the amide side-chain of Asparagine 747 of TM4 (Figure 2). A hydroxyl group similarly forms hydrogen bonds to the protein, specifically to two serine residues (S805 and S809) of TM7 which form a hydrogen bonding network to other residues through their main chain atoms and a coordinated water molecule (omitted for clarity) (Figure 3). The interactions between Mavoglurant andmGlu<sub>5</sub> involved TM helices that were not previously stabilized by any strong interactions, introducing a new level of stability that favors the inactive conformation of the protein and hence decrease activity<ref name="Primary">PMID: 25042998 </ref>. | The bicyclic ring system of the drug is surrounded by a pocket of mainly hydrophobic residues including Val 806, Met 802, Phe 788, Trp 785, Leu 744, Ile 651, Pro 655 and Asn 747<ref name="Primary">PMID: 25042998 </ref> (Figure 1). The carbamate tail of mavoglurant forms a hydrogen bond through its carbonyl oxygen to the amide side-chain of Asparagine 747 of TM4 (Figure 2). A hydroxyl group similarly forms hydrogen bonds to the protein, specifically to two serine residues (S805 and S809) of TM7 which form a hydrogen bonding network to other residues through their main chain atoms and a coordinated water molecule (omitted for clarity) (Figure 3). The interactions between Mavoglurant andmGlu<sub>5</sub> involved TM helices that were not previously stabilized by any strong interactions, introducing a new level of stability that favors the inactive conformation of the protein and hence decrease activity<ref name="Primary">PMID: 25042998 </ref>. | ||
[[Image:Mav_Hydrophobic_pocket.png | | [[Image:Mav_Hydrophobic_pocket.png |500 px|left|thumb|Figure 1.Hydrophobic Pocket Surrounding Mavoglurant]] | ||
[[Image:Mav_HB_1.1.png| | [[Image:Mav_HB_1.1.png|500 px|left|thumb|Figure 2.Hydrogen Bonding interactions between protein and Mavoglurant]] | ||
[[Image:Mav_HB_2.png| | [[Image:Mav_HB_2.png|500 px|left|thumb|Figure 3. Further Hydrogen Bonding between protein and Mavoglurant]] | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
