User:Anat Levit/Sandbox 1: Difference between revisions
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Based on this analysis, we defined the core residues which line the <scene name='User:Anat_Levit/Sandbox_1/Pkr1_consensus/2' target='PROKR1'>PROKR1</scene> and <scene name='User:Anat_Levit/Sandbox_1/Pkr2_consensus/2' target='PROKR2'>PROKR2</scene> binding pocket (the selected residues appear in at least two of the superpositions described). The pockets of the two receptors are almost identical, except for the additional Tyr140 and Glu319 residues in PROKR2. Tyr140 is known to be mutated in Kallmann syndrome. The p.Y140X nonsense mutation probably results in a PROKR2 with complete loss of function through the generation of an aberrant transcript that can be unstable or encodes for a truncated protein, lacking the carboxyl terminal domain. | Based on this analysis, we defined the core residues which line the <scene name='User:Anat_Levit/Sandbox_1/Pkr1_consensus/2' target='PROKR1'>PROKR1</scene> and <scene name='User:Anat_Levit/Sandbox_1/Pkr2_consensus/2' target='PROKR2'>PROKR2</scene> binding pocket (the selected residues appear in at least two of the superpositions described). The pockets of the two receptors are almost identical, except for the additional Tyr140 and Glu319 residues in PROKR2. Tyr140 is known to be mutated in Kallmann syndrome. The p.Y140X nonsense mutation probably results in a PROKR2 with complete loss of function through the generation of an aberrant transcript that can be unstable or encodes for a truncated protein, lacking the carboxyl terminal domain. | ||
===Conclusion=== | ===Conclusion=== | ||
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This has also been observed in other subfamilies of GPCRs (such as dopamine, serotonin, histamine and the adrenergic receptors) and may probably explain the difficulty in obtaining potent subtype-selective compounds in pharmaceutical discovery programs. | This has also been observed in other subfamilies of GPCRs (such as dopamine, serotonin, histamine and the adrenergic receptors) and may probably explain the difficulty in obtaining potent subtype-selective compounds in pharmaceutical discovery programs. | ||
<applet load='PKR2_model1.pdb' size='300' frame='true' name='PROKR2' align='right' caption='Human PROKR2' SCENE='User:Anat_Levit/Sandbox_1/Pkr2_2rh1_residues/2'> | <applet load='PKR2_model1.pdb' size='300' frame='true' name='PROKR2' align='right' caption='Human PROKR2' SCENE='User:Anat_Levit/Sandbox_1/Pkr2_2rh1_residues/2'> | ||
For more information about our lab, please visit us at [http://departments.agri.huji.ac.il/biochemfoodsci722/teachers/niv_masha/index.htm HUJI]. | |||