Sandbox Reserved 1703: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Jaime Prilusky, Ashley R. Wilkinson, R. Jeremy Johnson

@@ Line 24: / Line 24: @@
 ===PAM and NAM Bound Form===
-A positive allosteric modulator (PAM) or a negative allosteric modulator (NAM) can bind to mGlu2. PAM and NAM induce different conformational changes, which result in different outcomes. <scene name='90/904308/Pam/3'>PAM binds</scene> to the receptor, induces conformational changes, which helps to promote greater affinity for G protein binding. PAM binds in a binding pocket that is created by helices III, V, VI, VII in the <scene name='90/904307/Tmd_helices/4'>TMD</scene>. Within helix VI, the hydrophobic is is composed of W773, F776, L777, and F780. Due to spatial hindrance, helix VI is shifted downward, causing conformational changes. NAM, however, reduces the affinity for G protein binding. NAM binds to the same binding pocket as PAM and also interacts with residue W773, but NAM occupies the binding site a little deeper than PAM. This causes NAM to push the side chain of W773 towards helix VII<ref name="Lin"/>.
+A positive allosteric modulator (PAM) or a negative allosteric modulator (NAM) can bind to mGlu2. PAM and NAM induce different conformational changes, which result in different outcomes. <scene name='90/904308/Pam/3'>PAM binds</scene> to the receptor, induces conformational changes, which helps to promote greater affinity for G protein binding. PAM binds in a binding pocket that is created by helices III, V, VI, VII in the <scene name='90/904307/Tmd_helices/4'>TMD</scene>. Within helix VI, the hydrophobic binding is composed of W773, F776, L777, and F780. Due to spatial hindrance caused by the binding of PAM, helix VI is shifted downward, causing conformational changes that increase G-protein binding affinity. NAM, however, reduces the affinity for G protein binding. NAM binds to the same binding pocket as PAM and also interacts with residue W773, but NAM occupies the binding site a little deeper than PAM. This causes NAM to push the side chain of W773 towards helix VII<ref name="Lin"/>.
 [[Image:PAM binding pocket correct.png |250px|right|thumb|'''Figure 4.'''PAM located binding pocket. PAM, JNJ-40411813, is shown in magenta and colored by atom type, four labelled binding helices (III, V, VI, and VII) create the binding pocket in the 7TM region for PAM binding. PAM binding promotes G-protein activation by mGLu2.]]