Sandbox Reserved 1652: Difference between revisions

The pocket size characteristics of the TRPV1-RTX allow the installation of large structures such as the RTX : The '''sub-pocket''' near <scene name='86/868185/Y511/2'>Y511</scene> is shallow in the TRPV1-RTX because <scene name='86/868185/Y511/2'>Y511</scene> and <scene name='86/868185/E570/2'>E570</scene> are close and <scene name='86/868185/I569/1'>I569</scene> is oriented towards the vanilloid pocket.

The sub-pocket near <scene name='86/868185/L669/1'>L669</scene>, <scene name='86/868185/V583/1'>V583</scene> and <scene name='86/868185/F587/1'>F587</scene> is wide due to the projection of these amino acids out of the vanilloid pocket. This sub-pocket accommodates the [https://en.wikipedia.org/wiki/Diterpene diterpene] group of the RTX.

However, the orientation of <scene name='86/868185/L515/1'>L515</scene> and <scene name='86/868185/M547/1'>M547</scene> makes this region of the vanilloid pocket narrow, which considerably limits the nature of the fragments tolerated.

The aromatic part of resiniferatoxin is located deeper in the sub-pocket near <scene name='86/868185/Y511/2'>Y511</scene> and is oriented almost parallel to the aromatic side chain of <scene name='86/868185/Y511/2'>Y511</scene>, so it establishes a strong interaction π-π. The aromatic hydroxyl and methoxy groups of the RTX form strong hydrogen bonds with <scene name='86/868185/E570/2'>E570</scene>, <scene name='86/868185/R557/1'>R557</scene> and <scene name='86/868185/S512/1'>S512</scene>. The ester group is linked to <scene name='86/868185/Y511/2'>Y511</scene> and <scene name='86/868185/T550/2'>T550</scene> by hydrogen bonds.<ref>K. Elokely et al., « Understanding TRPV1 activation by ligands: Insights from the binding modes of capsaicin and resiniferatoxin », Proc. Natl. Acad. Sci., vol. 113, no 2, p. E137‑E145, janv. 2016, doi:10.1073/pnas.1517288113.</ref>