Sandbox Reserved 190 - Revision history

Kelly Maddalone at 23:33, 23 April 2014

Kelly Maddalone — Wed, 23 Apr 2014 23:33:40 GMT

←Older revision		Revision as of 23:33, 23 April 2014
Line 8:		Line 8:

	==Inhibitors of PPT-1==		==Inhibitors of PPT-1==
-	'''<scene name='43/436866/Overall-3-rainbow/1'>PPT-1</scene>''' is a lysosomal enzyme which had a serine lipase consensus sequence; a key characteristic of lysosomal enzymes. Despite having a serine lipase consensus sequence, PPT-1, is not deactivated by phenylmethylsulfonyl fluoride (PMSF), a common serine-modifying reagent. <scene name='58/580839/Hdsf_by_itself/1'>Hexadecylsulfonylfluoride</scene> (HDSF) is a serine-modifying reagent that is able to inhibit the actions of PPT1 <scene name='58/580839/Basic-hdsf-nosurface/4'>by binding to PPT-1</scene>. Unlike other inhibitors, <scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF is able to fit in the narrow, hydrophobic groove of PPT-1</scene> leading away from the active site of PPT-1. PMSF is unable to fit into this small narrow groove due to steric constraints that relate to the unique structure of the substrate-binding site of PPT1. The sulphur of HDSF will <scene name='58/580839/~~Hdsf_bound_to_Ser~~-115-best/1'>bind to SER-115 in the active site of PPT-1</scene> via a sulponylation reaction and thus will inhibit the actions of PPT-1.	+	'''<scene name='43/436866/Overall-3-rainbow/1'>PPT-1</scene>''' is a lysosomal enzyme which had a serine lipase consensus sequence; a key characteristic of lysosomal enzymes. Despite having a serine lipase consensus sequence, PPT-1, is not deactivated by phenylmethylsulfonyl fluoride (PMSF), a common serine-modifying reagent. <scene name='58/580839/Hdsf_by_itself/1'>Hexadecylsulfonylfluoride</scene> (HDSF) is a serine-modifying reagent that is able to inhibit the actions of PPT1 <scene name='58/580839/Basic-hdsf-nosurface/4'>by binding to PPT-1</scene>. Unlike other inhibitors, <scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF is able to fit in the narrow, hydrophobic groove of PPT-1</scene> leading away from the active site of PPT-1. PMSF is unable to fit into this small narrow groove due to steric constraints that relate to the unique structure of the substrate-binding site of PPT1. The sulphur of HDSF will <scene name='58/580839/Hdsf_bound_to_ser-115-best/1'>bind to SER-115 in the active site of PPT-1</scene> via a sulponylation reaction and thus will inhibit the actions of PPT-1.
		+


Line 45:		Line 46:

	<scene name='58/580839/Hdsf_bound_to_ser-115-best/1'>bind to SER-115 in the active site of PPT-1</scene>		<scene name='58/580839/Hdsf_bound_to_ser-115-best/1'>bind to SER-115 in the active site of PPT-1</scene>
		+
	<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>		<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>

Kelly Maddalone at 00:04, 3 April 2014

Kelly Maddalone — Thu, 03 Apr 2014 00:04:54 GMT

←Older revision		Revision as of 00:04, 3 April 2014
Line 13:		Line 13:
	==Disease Associated With PPT-1==		==Disease Associated With PPT-1==

-	Infantile Neuronal Ceroid Lipofuscinosis (INCL) is a recessively inherited disease that is associated with a ~~decreases~~ in PPT-1 activity due to mutations of the PPT-1 enzyme. Onset of symptoms which include retinal blindness, ataxia, seizures, and cortical atrophy of the brain, begin 1-2 years after birth. Death typically occurs between the ages of 8-11. Several mutations in the 1p32 chromosome have been identified to cause INCL.	+	Infantile Neuronal Ceroid Lipofuscinosis (INCL) is a recessively inherited disease that is associated with a decrease in PPT-1 activity due to mutations of the PPT-1 enzyme. Onset of symptoms which include retinal blindness, ataxia, seizures, and cortical atrophy of the brain, begin 1-2 years after birth. Death typically occurs between the ages of 8-11. Several mutations in the ''1p32'' chromosome have been identified to cause INCL.
	[[Image:All_mutations.jpg\|100px\|right\|thumb\|Mutations Associated with INCL]]		[[Image:All_mutations.jpg\|100px\|right\|thumb\|Mutations Associated with INCL]]

	Juvenile NCL (JNCL) and Late-infantile NCL (LINCL)are less severe forms of INCL in which onset of symptoms occur much later in life, between the ages of 30-40. The mutations associated with JNCL and LINCL occur away from the active site of PPT-1 resulting in a higher activity of the PPT-1 enzyme. A common mutation associated with JNCL and LINCL involves the mutation of Thr-75.		Juvenile NCL (JNCL) and Late-infantile NCL (LINCL)are less severe forms of INCL in which onset of symptoms occur much later in life, between the ages of 30-40. The mutations associated with JNCL and LINCL occur away from the active site of PPT-1 resulting in a higher activity of the PPT-1 enzyme. A common mutation associated with JNCL and LINCL involves the mutation of Thr-75.
-	~~IMAGE!!!!~~	+	[[Image:Thr-_mut.png\|200px\|right\|thumb\|Common Mutation associated with JNCL and LINCL involve mutations Far Away From Active Site]]

-	(Bellizzi J. Widom J. Kemp. Lu J. Das K. Hofmann L. Jon Clardy J. 2000. The crystal structure of palmitoyl protein thioesterase1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Biochemistry. 97: 4573-4578)	+	(Bellizzi J. Widom J. Kemp. Lu J. Das K. Hofmann L. Jon Clardy J. 2000. The crystal structure of palmitoyl protein thioesterase1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Biochemistry. 97: 4573-4578)

Kelly Maddalone at 23:54, 2 April 2014

Kelly Maddalone — Wed, 02 Apr 2014 23:54:39 GMT

←Older revision		Revision as of 23:54, 2 April 2014
Line 14:		Line 14:

	Infantile Neuronal Ceroid Lipofuscinosis (INCL) is a recessively inherited disease that is associated with a decreases in PPT-1 activity due to mutations of the PPT-1 enzyme. Onset of symptoms which include retinal blindness, ataxia, seizures, and cortical atrophy of the brain, begin 1-2 years after birth. Death typically occurs between the ages of 8-11. Several mutations in the 1p32 chromosome have been identified to cause INCL.		Infantile Neuronal Ceroid Lipofuscinosis (INCL) is a recessively inherited disease that is associated with a decreases in PPT-1 activity due to mutations of the PPT-1 enzyme. Onset of symptoms which include retinal blindness, ataxia, seizures, and cortical atrophy of the brain, begin 1-2 years after birth. Death typically occurs between the ages of 8-11. Several mutations in the 1p32 chromosome have been identified to cause INCL.
		+	[[Image:All_mutations.jpg\|100px\|right\|thumb\|Mutations Associated with INCL]]

	Juvenile NCL (JNCL) and Late-infantile NCL (LINCL)are less severe forms of INCL in which onset of symptoms occur much later in life, between the ages of 30-40. The mutations associated with JNCL and LINCL occur away from the active site of PPT-1 resulting in a higher activity of the PPT-1 enzyme. A common mutation associated with JNCL and LINCL involves the mutation of Thr-75.		Juvenile NCL (JNCL) and Late-infantile NCL (LINCL)are less severe forms of INCL in which onset of symptoms occur much later in life, between the ages of 30-40. The mutations associated with JNCL and LINCL occur away from the active site of PPT-1 resulting in a higher activity of the PPT-1 enzyme. A common mutation associated with JNCL and LINCL involves the mutation of Thr-75.
	IMAGE!!!!		IMAGE!!!!

-	(Bellizzi J. Widom J. Kemp. Lu J. Das K. Hofmann L. Jon Clardy J. 2000. The crystal structure of palmitoyl protein thioesterase1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Biochemistry. 97: 4573-4578)	+	(Bellizzi J. Widom J. Kemp. Lu J. Das K. Hofmann L. Jon Clardy J. 2000. The crystal structure of palmitoyl protein thioesterase1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Biochemistry. 97: 4573-4578)



-	Unfortunately not much is known on how to treat INCL. However, in both JNCL and LINCL activity of PPT-1~~, there is~~ only a ~~small,~~ 2%~~, increase in PPT-1~~ activity compared to normal PPT-1 activity. This suggests that a small increase in activity of PPT-1 may aid in delaying the symptoms associated with INCL. One way in which to increase the activity of PPT-1 is to use protein chaperons that help refold PPT-1 in the endoplasmic reticulm. Although this is not a cure for INCL, by increasing the activity of PPT-1 the life expectancy for individuals with INCL can be greatly increased.	+	Unfortunately not much is known on how to treat INCL. However, in both JNCL and LINCL activity of PPT-1 has only a 2% activity rate compared to normal PPT-1 activity. This suggests that a small increase in activity of PPT-1 may aid in delaying the symptoms associated with INCL. One way in which to increase the activity of PPT-1 is to use protein chaperons that help refold PPT-1 in the endoplasmic reticulm. Although this is not a cure for INCL, by increasing the activity of PPT-1 the life expectancy for individuals with INCL can be greatly increased.

Kelly Maddalone at 19:40, 2 April 2014

Kelly Maddalone — Wed, 02 Apr 2014 19:40:23 GMT

←Older revision		Revision as of 19:40, 2 April 2014
Line 9:		Line 9:
	==Inhibitors of PPT-1==		==Inhibitors of PPT-1==
	'''<scene name='43/436866/Overall-3-rainbow/1'>PPT-1</scene>''' is a lysosomal enzyme which had a serine lipase consensus sequence; a key characteristic of lysosomal enzymes. Despite having a serine lipase consensus sequence, PPT-1, is not deactivated by phenylmethylsulfonyl fluoride (PMSF), a common serine-modifying reagent. <scene name='58/580839/Hdsf_by_itself/1'>Hexadecylsulfonylfluoride</scene> (HDSF) is a serine-modifying reagent that is able to inhibit the actions of PPT1 <scene name='58/580839/Basic-hdsf-nosurface/4'>by binding to PPT-1</scene>. Unlike other inhibitors, <scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF is able to fit in the narrow, hydrophobic groove of PPT-1</scene> leading away from the active site of PPT-1. PMSF is unable to fit into this small narrow groove due to steric constraints that relate to the unique structure of the substrate-binding site of PPT1. The sulphur of HDSF will <scene name='58/580839/Hdsf_bound_to_Ser-115-best/1'>bind to SER-115 in the active site of PPT-1</scene> via a sulponylation reaction and thus will inhibit the actions of PPT-1.		'''<scene name='43/436866/Overall-3-rainbow/1'>PPT-1</scene>''' is a lysosomal enzyme which had a serine lipase consensus sequence; a key characteristic of lysosomal enzymes. Despite having a serine lipase consensus sequence, PPT-1, is not deactivated by phenylmethylsulfonyl fluoride (PMSF), a common serine-modifying reagent. <scene name='58/580839/Hdsf_by_itself/1'>Hexadecylsulfonylfluoride</scene> (HDSF) is a serine-modifying reagent that is able to inhibit the actions of PPT1 <scene name='58/580839/Basic-hdsf-nosurface/4'>by binding to PPT-1</scene>. Unlike other inhibitors, <scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF is able to fit in the narrow, hydrophobic groove of PPT-1</scene> leading away from the active site of PPT-1. PMSF is unable to fit into this small narrow groove due to steric constraints that relate to the unique structure of the substrate-binding site of PPT1. The sulphur of HDSF will <scene name='58/580839/Hdsf_bound_to_Ser-115-best/1'>bind to SER-115 in the active site of PPT-1</scene> via a sulponylation reaction and thus will inhibit the actions of PPT-1.
		+
		+
		+	==Disease Associated With PPT-1==
		+
		+	Infantile Neuronal Ceroid Lipofuscinosis (INCL) is a recessively inherited disease that is associated with a decreases in PPT-1 activity due to mutations of the PPT-1 enzyme. Onset of symptoms which include retinal blindness, ataxia, seizures, and cortical atrophy of the brain, begin 1-2 years after birth. Death typically occurs between the ages of 8-11. Several mutations in the 1p32 chromosome have been identified to cause INCL.
		+
		+	Juvenile NCL (JNCL) and Late-infantile NCL (LINCL)are less severe forms of INCL in which onset of symptoms occur much later in life, between the ages of 30-40. The mutations associated with JNCL and LINCL occur away from the active site of PPT-1 resulting in a higher activity of the PPT-1 enzyme. A common mutation associated with JNCL and LINCL involves the mutation of Thr-75.
		+	IMAGE!!!!
		+
		+	(Bellizzi J. Widom J. Kemp. Lu J. Das K. Hofmann L. Jon Clardy J. 2000. The crystal structure of palmitoyl protein thioesterase1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Biochemistry. 97: 4573-4578)
		+
		+
		+
		+	Unfortunately not much is known on how to treat INCL. However, in both JNCL and LINCL activity of PPT-1, there is only a small, 2%, increase in PPT-1 activity compared to normal PPT-1 activity. This suggests that a small increase in activity of PPT-1 may aid in delaying the symptoms associated with INCL. One way in which to increase the activity of PPT-1 is to use protein chaperons that help refold PPT-1 in the endoplasmic reticulm. Although this is not a cure for INCL, by increasing the activity of PPT-1 the life expectancy for individuals with INCL can be greatly increased.
		+
		+
		+
		+	(Dawson G. Schroeder C. Dawson P. 2010. Palmitoyl:protein thioesterase (PPT1) inhibitors can act as pharmacological chaperones in infantile Batten disease. Biochem and Biophys Research Comm. 395. 66-69.)
		+
		+
		+
		+
		+

Kelly Maddalone at 19:11, 2 April 2014

Kelly Maddalone — Wed, 02 Apr 2014 19:11:57 GMT

←Older revision		Revision as of 19:11, 2 April 2014
Line 5:		Line 5:
	Anything in this section will appear adjacent to the 3D structure and will be scrollable.		Anything in this section will appear adjacent to the 3D structure and will be scrollable.
	This is a default text for your page '''Sandbox Reserved 190'''		This is a default text for your page '''Sandbox Reserved 190'''
		+
		+
		+	==Inhibitors of PPT-1==
		+	'''<scene name='43/436866/Overall-3-rainbow/1'>PPT-1</scene>''' is a lysosomal enzyme which had a serine lipase consensus sequence; a key characteristic of lysosomal enzymes. Despite having a serine lipase consensus sequence, PPT-1, is not deactivated by phenylmethylsulfonyl fluoride (PMSF), a common serine-modifying reagent. <scene name='58/580839/Hdsf_by_itself/1'>Hexadecylsulfonylfluoride</scene> (HDSF) is a serine-modifying reagent that is able to inhibit the actions of PPT1 <scene name='58/580839/Basic-hdsf-nosurface/4'>by binding to PPT-1</scene>. Unlike other inhibitors, <scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF is able to fit in the narrow, hydrophobic groove of PPT-1</scene> leading away from the active site of PPT-1. PMSF is unable to fit into this small narrow groove due to steric constraints that relate to the unique structure of the substrate-binding site of PPT1. The sulphur of HDSF will <scene name='58/580839/Hdsf_bound_to_Ser-115-best/1'>bind to SER-115 in the active site of PPT-1</scene> via a sulponylation reaction and thus will inhibit the actions of PPT-1.
		+


	<scene name='58/580839/Hdsf_by_itself/1'>HDSF</scene>		<scene name='58/580839/Hdsf_by_itself/1'>HDSF</scene>

-	<scene name='58/580839/Basic-hdsf-nosurface/4'>~~HDSF binds~~ to PPT-1</scene>	+	<scene name='58/580839/Basic-hdsf-nosurface/4'>by binding to PPT-1</scene>

-	<scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF ~~can~~ fit in the ~~small~~ narrow groove of PPT-1</scene>	+	<scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF is able to fit in the narrow, hydrophobic groove of PPT-1</scene>

-	<scene name='58/580839/Hdsf_bound_to_ser-115/1'>~~HDSF Binds To~~ SER-115 in the active site of PPT-1</scene>	+	<scene name='58/580839/Hdsf_bound_to_ser-115/1'>binds to SER-115 in the active site of PPT-1</scene>

-	<scene name='58/580839/Hdsf_bound_to_ser-115-best/1'>~~HDSF Binds~~ to SER-115 </scene>	+	<scene name='58/580839/Hdsf_bound_to_ser-115-best/1'>bind to SER-115 in the active site of PPT-1</scene>
	<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>		<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>

Kelly Maddalone at 18:20, 28 March 2014

Kelly Maddalone — Fri, 28 Mar 2014 18:20:37 GMT

←Older revision		Revision as of 18:20, 28 March 2014
Line 15:		Line 15:
	<scene name='58/580839/Hdsf_bound_to_ser-115/1'>HDSF Binds To SER-115 in the active site of PPT-1</scene>		<scene name='58/580839/Hdsf_bound_to_ser-115/1'>HDSF Binds To SER-115 in the active site of PPT-1</scene>

		+	<scene name='58/580839/Hdsf_bound_to_ser-115-best/1'>HDSF Binds to SER-115 </scene>
	<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>		<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>

		+
		+	<scene name='58/580839/Hdsf_bound_to_ser-115-good/1'>TextToBeDisplayed</scene>
	</StructureSection>		</StructureSection>

Kelly Maddalone at 18:06, 28 March 2014

Kelly Maddalone — Fri, 28 Mar 2014 18:06:20 GMT

←Older revision		Revision as of 18:06, 28 March 2014
Line 1:		Line 1:
	==PPT-1==		==PPT-1==
-	<StructureSection load='~~3rec~~' size='340' side='right' caption='HDSF Binding' scene='>	+	<StructureSection load='3GRO' size='340' side='right' caption='HDSF Binding' scene=''>


Line 16:		Line 16:

	<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>		<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>
		+
		+	</StructureSection>

Kelly Maddalone at 18:04, 28 March 2014

Kelly Maddalone — Fri, 28 Mar 2014 18:04:58 GMT

←Older revision		Revision as of 18:04, 28 March 2014
Line 11:		Line 11:
	<scene name='58/580839/Basic-hdsf-nosurface/4'>HDSF binds to PPT-1</scene>		<scene name='58/580839/Basic-hdsf-nosurface/4'>HDSF binds to PPT-1</scene>

-	<scene name='58/580839/Basic-hdsf-surfacelook/1'>HDSF ~~is able to~~ fit ~~into~~ small groove</scene>	+	<scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF can fit in the small narrow groove of PPT-1</scene>

	<scene name='58/580839/Hdsf_bound_to_ser-115/1'>HDSF Binds To SER-115 in the active site of PPT-1</scene>		<scene name='58/580839/Hdsf_bound_to_ser-115/1'>HDSF Binds To SER-115 in the active site of PPT-1</scene>

	<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>		<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>

Kelly Maddalone at 18:02, 28 March 2014

Kelly Maddalone — Fri, 28 Mar 2014 18:02:03 GMT

←Older revision		Revision as of 18:02, 28 March 2014
Line 9:		Line 9:
	<scene name='58/580839/Hdsf_by_itself/1'>HDSF</scene>		<scene name='58/580839/Hdsf_by_itself/1'>HDSF</scene>

-	<scene name='58/580839/Basic-hdsf-nosurface/1'>HDSF ~~Binds~~ to ~~PPT1~~</scene>'	+	<scene name='58/580839/Basic-hdsf-nosurface/4'>HDSF binds to PPT-1</scene>

	<scene name='58/580839/Basic-hdsf-surfacelook/1'>HDSF is able to fit into small groove</scene>		<scene name='58/580839/Basic-hdsf-surfacelook/1'>HDSF is able to fit into small groove</scene>

Kelly Maddalone at 17:59, 28 March 2014

Kelly Maddalone — Fri, 28 Mar 2014 17:59:28 GMT

←Older revision		Revision as of 17:59, 28 March 2014
Line 14:		Line 14:

	<scene name='58/580839/Hdsf_bound_to_ser-115/1'>HDSF Binds To SER-115 in the active site of PPT-1</scene>		<scene name='58/580839/Hdsf_bound_to_ser-115/1'>HDSF Binds To SER-115 in the active site of PPT-1</scene>
		+
		+	<scene name='58/580839/Hdsf_with_ser/2'>HDSF with Ser-115</scene>