User:Harish Srinivas - Revision history

Harish Srinivas: Replacing page with '*User:Harish Srinivas/Sandbox 1'

Harish Srinivas — Sat, 09 Dec 2017 23:14:53 GMT

Replacing page with '*User:Harish Srinivas/Sandbox 1'

(Difference between revisions)

Harish Srinivas at 15:23, 8 December 2017

Harish Srinivas — Fri, 08 Dec 2017 15:23:09 GMT

(Difference between revisions)

Harish Srinivas at 17:31, 7 December 2017

Harish Srinivas — Thu, 07 Dec 2017 17:31:33 GMT

←Older revision		Revision as of 17:31, 7 December 2017
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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'''=

Harish Srinivas at 17:08, 7 December 2017

Harish Srinivas — Thu, 07 Dec 2017 17:08:42 GMT

←Older revision		Revision as of 17:08, 7 December 2017
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	[[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\|Fig2:Mutation F → L → 265]]

-	[[Image:Mutate w-f-7%-269 new.png\|~~700px~~\|centre\|Fig3:Mutation W → F → 269]]	+	[[Image:Mutate w-f-7%-269 new.png\|thumb\|500px\|centre\|Fig3:Mutation W → F → 269]]

Harish Srinivas at 17:07, 7 December 2017

Harish Srinivas — Thu, 07 Dec 2017 17:07:52 GMT

←Older revision		Revision as of 17:07, 7 December 2017
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	[[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\|Fig2:Mutation F → L → 265]]

-	[[Image:Mutate w-f-7%-269 new.png\|~~1000px~~\|centre\|Fig3:Mutation W → F → 269]]	+	[[Image:Mutate w-f-7%-269 new.png\|700px\|centre\|Fig3:Mutation W → F → 269]]

Harish Srinivas at 17:07, 7 December 2017

Harish Srinivas — Thu, 07 Dec 2017 17:07:14 GMT

←Older revision		Revision as of 17:07, 7 December 2017
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	[[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\|Fig2:Mutation F → L → 265]]

-	[[Image:Mutate w-l-8%-269 new.png~~\|thumb~~\|1000px\|centre\|Fig3:Mutation W → F → 269]]	+	[[Image:Mutate w-f-7%-269 new.png\|1000px\|centre\|Fig3:Mutation W → F → 269]]

Harish Srinivas at 04:02, 7 December 2017

Harish Srinivas — Thu, 07 Dec 2017 04:02:15 GMT

←Older revision		Revision as of 04:02, 7 December 2017
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	6.A Single Amino Acid Determines Lysophospholipid Specificity of the S1P1 (EDG1) and LPA1 (EDG2) Phospholipid Growth Factor Receptors*		6.A Single Amino Acid Determines Lysophospholipid Specificity of the S1P1 (EDG1) and LPA1 (EDG2) Phospholipid Growth Factor Receptors*
	Received for publication, July 31, 2001, and in revised form, October 15, 2001 Published, JBC Papers in Press, October 16, 2001, DOI 10.1074/jbc.M107301200		Received for publication, July 31, 2001, and in revised form, October 15, 2001 Published, JBC Papers in Press, October 16, 2001, DOI 10.1074/jbc.M107301200
-	De-an ~~Wang‡§~~, Zsolt ~~Lorincz‡§~~, Debra L. ~~Bautista¶�~~, Karoly ~~Liliom‡~~**, Gabor ~~Tigyi‡ ‡‡~~, and Abby L. ~~Parrill¶‡‡§§~~ From the ‡Department of Physiology, University of Tennessee Health Sciences Center Memphis, Memphis, Tennessee 38163 and the ¶Department of Chemistry and Computational Research on Materials Institute, The University of Memphis, Memphis, Tennessee 38152	+	De-an Wang, Zsolt Lorincz, Debra L. Bautista, Karoly Liliom**, Gabor Tigyi, and Abby L. Parrill From the ‡Department of Physiology, University of Tennessee Health Sciences Center Memphis, Memphis, Tennessee 38163 and the ¶Department of Chemistry and Computational Research on Materials Institute, The University of Memphis, Memphis, Tennessee 38152

Harish Srinivas at 03:23, 7 December 2017

Harish Srinivas — Thu, 07 Dec 2017 03:23:06 GMT

←Older revision		Revision as of 03:23, 7 December 2017
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	[[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\|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).]]

-	='''Therapeutic Target'''=	+	='''Therapeutic Target & Applications'''=
	1.The first oral treatment for relapsing multiple sclerosis, the nonselective sphingosine-1-phosphate receptor (S1PR) modulator fingolimod, led to identification of a pivotal role of sphingosine-1-phosphate and one of its five known receptors, S1P1R, in regulation of lymphocyte trafficking in multiple sclerosis. clinical utility of S1P1R modulation for treatment of various immune mediated disorders(11).		1.The first oral treatment for relapsing multiple sclerosis, the nonselective sphingosine-1-phosphate receptor (S1PR) modulator fingolimod, led to identification of a pivotal role of sphingosine-1-phosphate and one of its five known receptors, S1P1R, in regulation of lymphocyte trafficking in multiple sclerosis. clinical utility of S1P1R modulation for treatment of various immune mediated disorders(11).

	2.S1P1 is expressed in both hen and human ovarian tumors. S1P (the ligand for S1P1) has been implicated in the trafficking of immune cells. Immune cells are reported to be involved in the progression of tumors of various organs(10).		2.S1P1 is expressed in both hen and human ovarian tumors. S1P (the ligand for S1P1) has been implicated in the trafficking of immune cells. Immune cells are reported to be involved in the progression of tumors of various organs(10).
		+
		+	3.Development of a selective S1P1 receptor agonist, Syl930, as a potential therapeutic agent for autoimmune encephalitis(8).

Harish Srinivas at 03:19, 7 December 2017

Harish Srinivas — Thu, 07 Dec 2017 03:19:50 GMT

←Older revision		Revision as of 03:19, 7 December 2017
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	[[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\|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).]]
		+
		+	='''Therapeutic Target'''=
		+	1.The first oral treatment for relapsing multiple sclerosis, the nonselective sphingosine-1-phosphate receptor (S1PR) modulator fingolimod, led to identification of a pivotal role of sphingosine-1-phosphate and one of its five known receptors, S1P1R, in regulation of lymphocyte trafficking in multiple sclerosis. clinical utility of S1P1R modulation for treatment of various immune mediated disorders(11).
		+
		+	2.S1P1 is expressed in both hen and human ovarian tumors. S1P (the ligand for S1P1) has been implicated in the trafficking of immune cells. Immune cells are reported to be involved in the progression of tumors of various organs(10).
		+

	='''References'''=		='''References'''=
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	10.Sphingosine-1 phosphate receptor (S1p1), a critical receptor controlling human lymphocyte trafficking, is expressed in hen and human ovaries and ovarian tumors Michael J Bradaric1, Animesh Barua1,2,3, Krishna Penumatsa1, Yu Yi 1, Seby L Edassery1, Sameer Sharma2,4, Jacques S Abramowicz2, Janice M Bahr5, Judith L Luborsky1,2*		10.Sphingosine-1 phosphate receptor (S1p1), a critical receptor controlling human lymphocyte trafficking, is expressed in hen and human ovaries and ovarian tumors Michael J Bradaric1, Animesh Barua1,2,3, Krishna Penumatsa1, Yu Yi 1, Seby L Edassery1, Sameer Sharma2,4, Jacques S Abramowicz2, Janice M Bahr5, Judith L Luborsky1,2*
		+
		+
		+	11.Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases
		+	Daniele D’Ambrosio, Mark S. Freedman and Joerg Prinz

Harish Srinivas at 02:32, 7 December 2017

Harish Srinivas — Thu, 07 Dec 2017 02:32:56 GMT

←Older revision		Revision as of 02:32, 7 December 2017
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	='''Mutagenesis'''=		='''Mutagenesis'''=

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

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

-	[[Image:Mutate w-l-8%-269 new.png\|thumb\|1000px\|centre\|~~Fig~~: W → F → 269]]	+	[[Image:Mutate w-l-8%-269 new.png\|thumb\|1000px\|centre\|Fig3: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\|~~Fig~~: 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.]]	+	[[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).]]

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

-	[[Image:Immune system new.jpg\|thumb\|1000px\|centre\|~~Fig~~: 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. ]]	+	[[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'.jpg\|thumb\|1000px\|centre\|~~Fig~~: 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. ]]	+	[[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). ]]

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

-	[[Image:Nervous system'.jpg\|thumb\|1000px\|centre\|~~Fig~~: 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.]]	+	[[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).]]

	='''References'''=		='''References'''=