Neurofibromin: Difference between revisions
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The active site for GTP hydrolysis of Ras is located in the Gap-related domain of neurofibromin. The catalytic residues include R68, Q61, and Y32, as well as magnesium and water molecules. Arginine is referred to as an “arginine finger” because it points into the binding site of GTP to stabilize and orient the position of glutamine through a network of hydrogen bonds between water molecules. This arginine comes from the Gap-related domain of neurofibromin. When GDP is bound, glutamine is too far away to perform its catalytic action. Glutamine interacts with the gamma phosphate via a hydrogen bond created from an interaction between a water molecule and the gamma phosphate. When GTP is bound, tyrosine moves inward to face it. In the GDP bound form, tyrosine faces outward. | The active site for GTP hydrolysis of Ras is located in the Gap-related domain of neurofibromin. The catalytic residues include R68, Q61, and Y32, as well as magnesium and water molecules. Arginine is referred to as an “arginine finger” because it points into the binding site of GTP to stabilize and orient the position of glutamine through a network of hydrogen bonds between water molecules. This arginine comes from the Gap-related domain of neurofibromin. When GDP is bound, glutamine is too far away to perform its catalytic action. Glutamine interacts with the gamma phosphate via a hydrogen bond created from an interaction between a water molecule and the gamma phosphate. When GTP is bound, tyrosine moves inward to face it. In the GDP bound form, tyrosine faces outward. | ||
====Arginine Finger==== | ====Arginine Finger==== | ||
<scene name='90/904325/Arginine_finger_and_gdp/ | <scene name='90/904325/Arginine_finger_and_gdp/2'>The catalytic glutamine is too far away from the GDP substrate for any interaction to occur.</scene> | ||
<scene name='90/904325/Arginine_finger_and_gtp/ | <scene name='90/904325/Arginine_finger_and_gtp/2'>The arginine finger stabilizes the catalytic glutamine, assisting in cleavage of the 3rd phosphate group.</scene> | ||
====Conformations==== | ====Conformations==== | ||
Neurofibromin is a dimeric protein that is found in the cytoplasm. It exists in two conformations, <scene name='90/904326/Open_conformation/2'>open</scene> and <scene name='90/904326/Closed_conformation/2'>closed</scene> . The open conformation has one of the protomers in an auto-inhibited conformation and the other in an open conformation. In the <scene name='90/904326/Open_conformation_with_grd_hig/2'>open conformation</scene>, Ras is able to bind to the GRD neurofibromin. The <scene name='90/904326/Grd_closed_conformation/2'>closed conformation</scene> has both protomers in an autoinhibited conformation, which sterically hinders the binding of Ras to GRD. | Neurofibromin is a dimeric protein that is found in the cytoplasm. It exists in two conformations, <scene name='90/904326/Open_conformation/2'>open</scene> and <scene name='90/904326/Closed_conformation/2'>closed</scene> . The open conformation has one of the protomers in an auto-inhibited conformation and the other in an open conformation. In the <scene name='90/904326/Open_conformation_with_grd_hig/2'>open conformation</scene>, Ras is able to bind to the GRD neurofibromin. The <scene name='90/904326/Grd_closed_conformation/2'>closed conformation</scene> has both protomers in an autoinhibited conformation, which sterically hinders the binding of Ras to GRD. | ||
