User:Harish Srinivas: Difference between revisions

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One cluster of core contacts links transmembrane '''(TM) I, II, and VII, cluster 1''' consists of individual interaction groups.  '''The second cluster''' of interactions links '''TM II, III, and IV''' through a series of four interaction groups  and a frequently observed interaction between position  interact through a hydrogen bond between an Asn  or Ser  and the indole nitrogen of a Trp. '''A third cluster''' of conserved contacts links together TM helices III, VI, and VII in the vicinity of the S1P1 receptor ligand binding pocket. These positions maintain important contacts between '''TM VI and TM III''' through two side chain-mediated interactions.  Finally, '''cluster number four''' consists of three interactions that constrain '''TM V relative to TM III and one interaction between TM V and TM VI'''(4).
One cluster of core contacts links transmembrane '''(TM) I, II, and VII, cluster 1''' consists of individual interaction groups.  '''The second cluster''' of interactions links '''TM II, III, and IV''' through a series of four interaction groups  and a frequently observed interaction between position  interact through a hydrogen bond between an Asn  or Ser  and the indole nitrogen of a Trp. '''A third cluster''' of conserved contacts links together TM helices III, VI, and VII in the vicinity of the S1P1 receptor ligand binding pocket. These positions maintain important contacts between '''TM VI and TM III''' through two side chain-mediated interactions.  Finally, '''cluster number four''' consists of three interactions that constrain '''TM V relative to TM III and one interaction between TM V and TM VI'''(4).
[[Image:Rmsd values of class a gpcr new.jpg|thumb|300px|centre|Fig1: Plot of the RMSD values of the receptor family in comparison with S1P1 receptor. The dark gray values are core RMSD, and the light gray values are transmembrane domain RMSD(4).]]
[[Image:Rmsf values of tm region new.jpg|thumb|500px|centre|Fig2: Graph of the root mean square fluctuation over the set of GPCRs(4).]]


==''Exrtra-cellular region''==
==''Exrtra-cellular region''==
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='''Mutagenesis'''=
='''Mutagenesis'''=


                                     [[Image:Mutate f-l-5%-210 new.png|thumb|1000px|centre|Fig1:Mutation F → L → 210]]
                                     [[Image:Mutate f-l-5%-210 new.png|thumb|1000px|centre|Fig3: Mutation F → L → 210.]]


                                     [[Image:Muatef-l-8%-265 new.png|thumb|1000px|centre|Fig2:Mutation F → L → 265]]
                                     [[Image:Muatef-l-8%-265 new.png|thumb|1000px|centre|Fig4: Mutation F → L → 265.]]


                                     [[Image:Mutate w-f-7%-269 new.png|thumb|500px|centre|Fig3:Mutation W → F → 269]]
                                     [[Image:Mutate w-f-7%-269 new.png|thumb|500px|centre|Fig5: Mutation W → F → 269.]]




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==''Vascular and Lymphatic systems''==
==''Vascular and Lymphatic systems''==


           [[Image:Vascular and lymphatic systems new.jpg|thumb|1000px|centre|Fig4: Expression of S1PR and responses by endothelial cells Endothelial cells express S1P1, S1P2, and S1P3 protein. Endothelial cells may express different S1PR depending on activation status(1).]]
           [[Image:Vascular and lymphatic systems new.jpg|thumb|1000px|centre|Fig6: Expression of S1PR and responses by endothelial cells Endothelial cells express S1P1, S1P2, and S1P3 protein. Endothelial cells may express different S1PR depending on activation status(1).]]


==''Immune systems''==
==''Immune systems''==


                 [[Image:Immune system new.jpg|thumb|1000px|centre|Fig5:  Expression of S1PR and responses by cells of the acquired immune system. T cells express S1P1 and S1P4, B cells express S1P1, S1P2, S1P3, and S1P4, and natural killer (NK) cells express S1P1 and S1P5(1). ]]
                 [[Image:Immune system new.jpg|thumb|1000px|centre|Fig7:  Expression of S1PR and responses by cells of the acquired immune system. T cells express S1P1 and S1P4, B cells express S1P1, S1P2, S1P3, and S1P4, and natural killer (NK) cells express S1P1 and S1P5(1).]]




                                         [[Image:Immune'.jpg|thumb|1000px|centre|Fig6:  Expression of S1PR and responses by cells of the innate immune system. Monocytes and/or macrophages express S1P1-4, neutrophils express S1P1, S1P3, and S1P4, eosinophils and mast cells express all S1PR, and dendritic cells express S1P1, S1P3, and S1P4(1). ]]
                                         [[Image:Immune'.jpg|thumb|1000px|centre|Fig8:  Expression of S1PR and responses by cells of the innate immune system. Monocytes and/or macrophages express S1P1-4, neutrophils express S1P1, S1P3, and S1P4, eosinophils and mast cells express all S1PR, and dendritic cells express S1P1, S1P3, and S1P4(1).]]


==''Nervous systems''==
==''Nervous systems''==


                                     [[Image:Nervous system'.jpg|thumb|1000px|centre|Fig7:  Expression of S1PR and responses by neural cells.  Neural progenitors express S1P1 and S1P2, neurons express S1P1 and S1P3, oligodendrocytes express S1P1 and S1P5, and astrocytes express S1P1 and S1P2. S1P1 couples exclusively to Gαi. S1P2 and S1P3 can couple to GαI, Gα12/13, or Gαq, and S1P5 can couple to GαI or Gα12/13(1).]]
                                     [[Image:Nervous system'.jpg|thumb|1000px|centre|Fig9:  Expression of S1PR and responses by neural cells.  Neural progenitors express S1P1 and S1P2, neurons express S1P1 and S1P3, oligodendrocytes express S1P1 and S1P5, and astrocytes express S1P1 and S1P2. S1P1 couples exclusively to Gαi. S1P2 and S1P3 can couple to GαI, Gα12/13, or Gαq, and S1P5 can couple to GαI or Gα12/13(1).]]


='''Therapeutic Target & Applications'''=
='''Therapeutic Target & Applications'''=
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