Sandbox 121: Difference between revisions

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==='''Conformational Change'''===
==='''Conformational Change'''===
[[Image:B2AR-Binding_Pocket_OH.JPG|thumb|right|alt= Alt text| Models of  isoproternol binding to two B2AR structures. (a) Inactive B2AR: 4.78Å distance between the catechol-OH of the ligand and Ser207 of TM5  is too large for a H-bond. (b)  Active B2AR: A hydrogen bond distance of 2.17Å  between the catechol-OH of the ligand and Ser207  on TM5 is shown. |300px]]
 
[[Image:B2AR-Binding_Pocket_clash.JPG|thumb|right|alt= Alt text| Model of carazolol binding to B2AR structure. (a) Active B2AR: there is a steric clash between the ligand and Ser207 of TM5.  (b)Inactive B2AR: carazolol in B2AR fits perfectly and blocks the agonist from entering  the binding pocket. |300px]]


When an agonist is in the binding pocket a 2.1Å inward movement of TM5 at Ser207 is observed. This bulge at ser207 allows for a hydrogen bond between the ligand and the receptor. This interaction appears to be a key event in activation.  
When an agonist is in the binding pocket a 2.1Å inward movement of TM5 at Ser207 is observed. This bulge at ser207 allows for a hydrogen bond between the ligand and the receptor. This interaction appears to be a key event in activation.  
After the agonist binds, there is a rearrangement of interactions between residues located beneath the binding pocket that contributes to a rotation and outward movement of TM6 at Phe282. This change is associated with the breaking of the ionic lock between Glu268 in TM6 and Arg131 in TM3, resulting in an 11.4Å outward movement of the helix at the cytoplasmic face.  
After the agonist binds, there is a rearrangement of interactions between residues located beneath the binding pocket that contributes to a rotation and outward movement of TM6 at Phe282. This change is associated with the breaking of the ionic lock between Glu268 in TM6 and Arg131 in TM3, resulting in an 11.4Å outward movement of the helix at the cytoplasmic face.  
 
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|[[Image:B2AR-Binding_Pocket_OH.JPG|thumb|left|alt= Alt text| Models of  isoproternol binding to two B2AR structures. (a) Inactive B2AR: 4.78Å distance between the catechol-OH of the ligand and Ser207 of TM5  is too large for a H-bond. (b)  Active B2AR: A hydrogen bond distance of 2.17Å  between the catechol-OH of the ligand and Ser207  on TM5 is shown. |300px]]
|[[Image:B2AR-Binding_Pocket_clash.JPG|thumb|left|alt= Alt text| Model of carazolol binding to B2AR structure. (a) Active B2AR: there is a steric clash between the ligand and Ser207 of TM5. (b)Inactive B2AR: carazolol in B2AR fits perfectly and blocks the agonist from entering  the binding pocket. |300px]]
|}
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==='''Molecular Morph'''===
==='''Molecular Morph'''===
The coordinates for molecular morphs between inactive state of B2AR (2rh1) and active state (3p0g) were generated using iPyMOL and eMovie (http://www.weizmann.ac.il/ISPC/eMovie.html). Morphs, a series of 10 linear interpolations between a starting and finishing model, are useful when viewing the transition of a conformational change. This model of B2AR using morphs should not be thought of as precise animation of conformational changes upon activation but rather as a comparison of the inactive state to the active state.
The coordinates for molecular morphs between inactive state of B2AR (2rh1) and active state (3p0g) were generated using iPyMOL and eMovie (http://www.weizmann.ac.il/ISPC/eMovie.html). Morphs, a series of 10 linear interpolations between a starting and finishing model, are useful when viewing the transition of a conformational change. This model of B2AR using morphs should not be thought of as precise animation of conformational changes upon activation but rather as a comparison of the inactive state to the active state.
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