User:Anat Levit/Sandbox 1: Difference between revisions

Line 72:

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. ~~This high conservation may explain the very similar affinity~~ of the ~~receptors to their cognate ligands, and has also been observed in other subfamilies~~ of ~~GPCRs (such as dopamine, serotonin~~, ~~histamine and the adrenergic receptors). This may probably explain~~ the ~~difficulty in obtaining potent subtype-selective compounds in pharmaceutical discovery programs~~.

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.

Revision as of 12:58, 8 October 2009 view source Anat Levit (talk \| contribs) 77 edits No edit summary ← Older edit		Revision as of 13:29, 8 October 2009 view source Anat Levit (talk \| contribs) 77 edits No edit summary Newer edit →
Line 72:		Line 72:


	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. ~~This high conservation may explain the very similar affinity~~ of the ~~receptors to their cognate ligands, and has also been observed in other subfamilies~~ of ~~GPCRs (such as dopamine, serotonin~~, ~~histamine and the adrenergic receptors). This may probably explain~~ the ~~difficulty in obtaining potent subtype-selective compounds in pharmaceutical discovery programs~~.		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.


	<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'>