Sandbox Reserved 1161 - Revision history

Connor Coatney at 12:56, 30 March 2016

Connor Coatney — Wed, 30 Mar 2016 12:56:12 GMT

←Older revision		Revision as of 12:56, 30 March 2016
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	== Function and Pathway ==		== Function and Pathway ==

-	It all begins with glutamate binding to the venus fly trap domain. The signal transduction goes across the cystine-rich domain to the TMD. Next the dimerization of the TMD occurs. This activates the Gq/11 pathway, which activates phspholipase Cβ. The active phospholipase Cβ performs hydrolysis on phosphotinositides and generates inositol 1,4,5-trisphosphate and diacyl-glycerol. This results in calcium mobilization and activation of protein kinase C. (Niswender, Colleen M..(2010). "Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease." Annu. Rev. Pharmacol. Toxicol. Annual Review of Pharmacology and Toxicology 50.1: 295-322.)	+	It all begins with glutamate binding to the venus fly trap domain. The signal transduction goes across the cystine-rich domain to the TMD. Next the dimerization of the TMD occurs. This activates the Gq/11 pathway, which activates phspholipase Cβ. The active phospholipase Cβ performs hydrolysis on phosphotinositides and generates [https://pubchem.ncbi.nlm.nih.gov/compound/439456#section=Top/ inositol 1,4,5-trisphosphate] and [https://en.wikipedia.org/wiki/Diglyceride/ diacyl-glycerol]. This results in calcium mobilization and activation of protein kinase C. (Niswender, Colleen M..(2010). "Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease." Annu. Rev. Pharmacol. Toxicol. Annual Review of Pharmacology and Toxicology 50.1: 295-322.)

	== Disease ==		== Disease ==

Connor Coatney at 02:46, 30 March 2016

Connor Coatney — Wed, 30 Mar 2016 02:46:32 GMT

←Older revision		Revision as of 02:46, 30 March 2016
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	In the 7 transmembrane domain (TMD), <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the TMD.		In the 7 transmembrane domain (TMD), <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the TMD.

-	The variation can be seen in positioning of alpha helices. Class C has seemingly less space for mavoglurant to enter compared to Class A and F (Wu). The binding of mavoglurant is seen to be varied in different locations due to helix position (Dore).	+	The variation can be seen in positioning of alpha helices. Class C has seemingly less space for [https://fragilex.org/2014/research/news-reports-and-commentaries/novartis-announces-results-of-mavoglurant-mglur5-afq056-clinical-trials-and-the-conclusion-of-the-long-term-extension-study/ mavoglurant] to enter compared to Class A and F (Wu). The binding of mavoglurant is seen to be varied in different locations due to helix position (Dore).

Connor Coatney at 02:31, 30 March 2016

Connor Coatney — Wed, 30 Mar 2016 02:31:19 GMT

←Older revision		Revision as of 02:31, 30 March 2016
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	[[Image: Organic with clipped surface.png\|100 px\|left\|thumb\|Cross section view of mavoglurant in the binding pocket]]		[[Image: Organic with clipped surface.png\|100 px\|left\|thumb\|Cross section view of mavoglurant in the binding pocket]]

-	In the 7 transmembrane (~~7TM~~) ~~domain~~, <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the ~~7TM Domain~~.	+	In the 7 transmembrane domain (TMD), <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the TMD.

	The variation can be seen in positioning of alpha helices. Class C has seemingly less space for mavoglurant to enter compared to Class A and F (Wu). The binding of mavoglurant is seen to be varied in different locations due to helix position (Dore).		The variation can be seen in positioning of alpha helices. Class C has seemingly less space for mavoglurant to enter compared to Class A and F (Wu). The binding of mavoglurant is seen to be varied in different locations due to helix position (Dore).
Line 23:		Line 23:
	== Function and Pathway ==		== Function and Pathway ==

-	It all begins with glutamate binding to the venus fly trap domain. The signal transduction goes across the cystine-rich domain to the ~~7TM~~. Next the dimerization of the ~~7TM~~ occurs. This activates the Gq/11 pathway, which activates phspholipase Cβ. The active phospholipase Cβ performs hydrolysis on phosphotinositides and generates inositol 1,4,5-trisphosphate and diacyl-glycerol. This results in calcium mobilization and activation of protein kinase C. (Niswender, Colleen M..(2010). "Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease." Annu. Rev. Pharmacol. Toxicol. Annual Review of Pharmacology and Toxicology 50.1: 295-322.)	+	It all begins with glutamate binding to the venus fly trap domain. The signal transduction goes across the cystine-rich domain to the TMD. Next the dimerization of the TMD occurs. This activates the Gq/11 pathway, which activates phspholipase Cβ. The active phospholipase Cβ performs hydrolysis on phosphotinositides and generates inositol 1,4,5-trisphosphate and diacyl-glycerol. This results in calcium mobilization and activation of protein kinase C. (Niswender, Colleen M..(2010). "Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease." Annu. Rev. Pharmacol. Toxicol. Annual Review of Pharmacology and Toxicology 50.1: 295-322.)

	== Disease ==		== Disease ==

Connor Coatney at 02:28, 30 March 2016

Connor Coatney — Wed, 30 Mar 2016 02:28:08 GMT

←Older revision		Revision as of 02:28, 30 March 2016
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	== Human metabotropic glutamate receptor 5 transmembrane domain ==		== Human metabotropic glutamate receptor 5 transmembrane domain ==
	<StructureSection load='4oo9' size='350' frame='true' side='right' caption='Human metabotropic glutamate receptor 5 transmembrane domain' <'scene='(Ionic_lock)'>		<StructureSection load='4oo9' size='350' frame='true' side='right' caption='Human metabotropic glutamate receptor 5 transmembrane domain' <'scene='(Ionic_lock)'>
-	~~The~~ Human metabotropic glutamate receptor 5 transmembrane domain is a	+
		+	<StructureSection load='4oo9' size='300' frame='true' side='right' caption='Human metabotropic glutamate receptor 5 transmembrane domain' scene='72/721531/Protien_clean_sce/1'>
		+	Receiving and responding to extracellular messages is critical to the proper function of the nervous system. Glutamate is the major excitory neurotransmitter of the CNS, and metabotropic glutamate receptor 5 will play a major role in glutamate signaling. Metabotropic glutamate receptor 5 transmembrane domain is a homodimeric [[GPCR]] that resides in the cellular membrane <ref name="Dore" />. This domain is a member of the Class C GPCR family and can further be categorized into the Group I subgroup. The transmembrane domain will signal through a Gq/11 pathway. mGlu5 will bind glutamate to the extracellular Venus flytrap domain and the signal will be transduced across the membrane to a heterotrimeric G protein, which will ultimately lead to calcium release and activation of PKC. This will elicit a excitory post-synaptic repose and modulate long term potentiation. Human metabotropic glutamate receptor 5 is found throughout the central nervous system. Areas containing high concentrations of this protein are often involved involved in emotions and higher cognition<ref name="Niswender" />. The localization of mGlu5 in the CNS and the presence of multiple domains makes mGlu5 a possible target for treating schizophrenia,[http://www.fragilex.org/fragile-x/fragile-x-syndrome/ Fragile X], depression, anxiety,and Alzheimer's disease<ref name="Wu" />.
		+
		+	<ref name="Dore">PMID: 25042998</ref>

	== Structure ==		== Structure ==

Connor Coatney at 02:22, 30 March 2016

Connor Coatney — Wed, 30 Mar 2016 02:22:55 GMT

←Older revision		Revision as of 02:22, 30 March 2016
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	In the 7 transmembrane (7TM) domain, <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the 7TM Domain.		In the 7 transmembrane (7TM) domain, <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the 7TM Domain.

-	~~[[Image: Screen_Shot_2016-03-29_at_9~~.33.~~05_PM~~.~~png\|100 px\|left\|thumb\|7TM comparison among classes]]~~	+	The variation can be seen in positioning of alpha helices. Class C has seemingly less space for mavoglurant to enter compared to Class A and F (Wu). The binding of mavoglurant is seen to be varied in different locations due to helix position (Dore).
		+
		+
	== Function and Pathway ==		== Function and Pathway ==
		+
		+	It all begins with glutamate binding to the venus fly trap domain. The signal transduction goes across the cystine-rich domain to the 7TM. Next the dimerization of the 7TM occurs. This activates the Gq/11 pathway, which activates phspholipase Cβ. The active phospholipase Cβ performs hydrolysis on phosphotinositides and generates inositol 1,4,5-trisphosphate and diacyl-glycerol. This results in calcium mobilization and activation of protein kinase C. (Niswender, Colleen M..(2010). "Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease." Annu. Rev. Pharmacol. Toxicol. Annual Review of Pharmacology and Toxicology 50.1: 295-322.)

	== Disease ==		== Disease ==

Connor Coatney at 01:47, 30 March 2016

Connor Coatney — Wed, 30 Mar 2016 01:47:12 GMT

←Older revision		Revision as of 01:47, 30 March 2016
Line 13:		Line 13:

	In the 7 transmembrane (7TM) domain, <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the 7TM Domain.		In the 7 transmembrane (7TM) domain, <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the 7TM Domain.
		+
		+	[[Image: Screen_Shot_2016-03-29_at_9.33.05_PM.png\|100 px\|left\|thumb\|7TM comparison among classes]]
	== Function and Pathway ==		== Function and Pathway ==

Connor Coatney at 01:19, 30 March 2016

Connor Coatney — Wed, 30 Mar 2016 01:19:37 GMT

←Older revision		Revision as of 01:19, 30 March 2016
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	=== Extracellular Domain ===		=== Extracellular Domain ===

-	This is the <scene name='72/721532/Ecl_trail_1/7'>Extracellular Loops</scene> shows the extracellular loops (ECL) 1, 2, and 3 highlighted in purple. Additionally in the ECL domain, a <scene name='72/721532/Ecl_trail_1/6'>Disulfide Bond</scene> is attached to Helix 3 and the Amino Acid chain between Helix 5 and the N terminus. The disulfide bond is highlighted in yellow.	+	This is the <scene name='72/721532/Ecl_trail_1/7'>Extracellular Loops</scene> shows the extracellular loops (ECL) 1, 2, and 3 highlighted in purple. Additionally in the ECL domain, a <scene name='72/721532/Ecl_trail_1/6'>Disulfide Bond</scene> is attached to Helix 3 and the Amino Acid chain between Helix 5 and the N terminus. The disulfide bond is highlighted in yellow, and it is conserved in all classes of glutamate receptor 5 transmembrane domains.
-		+

	=== Binding Pocket ===		=== Binding Pocket ===

Connor Coatney at 15:48, 29 March 2016

Connor Coatney — Tue, 29 Mar 2016 15:48:33 GMT

←Older revision		Revision as of 15:48, 29 March 2016
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	=== Binding Pocket ===		=== Binding Pocket ===
-	[[Image: Organic with clipped surface.png\|100 px\|left\|thumb\|~~Figure Legend]]~~	+	[[Image: Organic with clipped surface.png\|100 px\|left\|thumb\|Cross section view of mavoglurant in the binding pocket]]
-		+
-	~~In the 7 transmembrane (7TM) domain, <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant.</scene> is~~ in the ~~7TM domain~~ pocket~~. Also, the lysozyme is attached to the intercellular region of the 7TM Domain.~~	+

		+	In the 7 transmembrane (7TM) domain, <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the 7TM Domain.
	== Function and Pathway ==		== Function and Pathway ==

Connor Coatney at 15:47, 29 March 2016

Connor Coatney — Tue, 29 Mar 2016 15:47:19 GMT

←Older revision		Revision as of 15:47, 29 March 2016
Line 7:		Line 7:
	=== Extracellular Domain ===		=== Extracellular Domain ===

-	This is the <scene name='72/721532/Ecl_trail_1/7'>Extracellular Loops</scene> shows the extracellular loops (ECL) 1, 2, and 3 highlighted in purple. Additionally in the ECL domain, a <scene name='72/721532/Ecl_trail_1/6'>Disulfide Bond</scene> is attached to Helix 3 and the Amino Acid chain between Helix 5 and the N terminus.	+	This is the <scene name='72/721532/Ecl_trail_1/7'>Extracellular Loops</scene> shows the extracellular loops (ECL) 1, 2, and 3 highlighted in purple. Additionally in the ECL domain, a <scene name='72/721532/Ecl_trail_1/6'>Disulfide Bond</scene> is attached to Helix 3 and the Amino Acid chain between Helix 5 and the N terminus. The disulfide bond is highlighted in yellow.


Line 13:		Line 13:
	[[Image: Organic with clipped surface.png\|100 px\|left\|thumb\|Figure Legend]]		[[Image: Organic with clipped surface.png\|100 px\|left\|thumb\|Figure Legend]]

-	<scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant ~~Mavoglurant~~ is in the ~~7 Transmembrane Domain Pocket~~. Also, the lysozyme is attached to the intercellular region of the ~~7 Transmembrane~~ Domain.~~</scene>~~	+	In the 7 transmembrane (7TM) domain, <scene name='72/721532/Mavoglurant_in_pocket/4'>Mavoglurant.</scene> is in the 7TM domain pocket. Also, the lysozyme is attached to the intercellular region of the 7TM Domain.

	== Function and Pathway ==		== Function and Pathway ==

Connor Coatney at 15:42, 29 March 2016

Connor Coatney — Tue, 29 Mar 2016 15:42:48 GMT

←Older revision		Revision as of 15:42, 29 March 2016
Line 7:		Line 7:
	=== Extracellular Domain ===		=== Extracellular Domain ===

-	This is the <scene name='72/721532/Ecl_trail_1/7'>Extracellular Loops ECL 1, 2, and 3 highlighted in purple</scene>	+	This is the <scene name='72/721532/Ecl_trail_1/7'>Extracellular Loops</scene> shows the extracellular loops (ECL) 1, 2, and 3 highlighted in purple. Additionally in the ECL domain, a <scene name='72/721532/Ecl_trail_1/6'>Disulfide Bond</scene> is attached to Helix 3 and the Amino Acid chain between Helix 5 and the N terminus.


-	<scene name='72/721532/Ecl_trail_1/6'>Disulfide Bond The Disulfide bond is attached to Helix 3 and the Amino Acid chain connected to Helix 5 and the N terminus</scene>
	=== Binding Pocket ===		=== Binding Pocket ===
	[[Image: Organic with clipped surface.png\|100 px\|left\|thumb\|Figure Legend]]		[[Image: Organic with clipped surface.png\|100 px\|left\|thumb\|Figure Legend]]