Sandbox 250 - Revision history

Allison Granberry at 23:02, 13 October 2011

Allison Granberry — Thu, 13 Oct 2011 23:02:54 GMT

←Older revision		Revision as of 23:02, 13 October 2011
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	7. Michal Harel, Weizmann Institute of Science		7. Michal Harel, Weizmann Institute of Science

-	8. Hostos Community College, Bronx, NY	+	8. Natural Sciences Department,Hostos Community College, Bronx, NY

	9. Malcolm Twist		9. Malcolm Twist

Joel L. Sussman: /* '''Background Information''' */

Joel L. Sussman — Thu, 13 Oct 2011 06:48:11 GMT

'''Background Information'''

←Older revision		Revision as of 06:48, 13 October 2011
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	==='''Background Information'''===		==='''Background Information'''===
-
	[[Image:AChE-Page-Cholinergic-Synapse.jpg\|thumb\|alt= Alt text\| Figure 2. Cholinergic Synapse \|375px]]		[[Image:AChE-Page-Cholinergic-Synapse.jpg\|thumb\|alt= Alt text\| Figure 2. Cholinergic Synapse \|375px]]
-

	When a nerve impulse reaches the presynaptic nerve terminal of a cholinergic synpase, it stimulates the release of the neurotransmitter, ACh (Figure 1), into the synaptic cleft. ACh diffuses across the cleft to the postsynaptic nerve terminal, where it binds reversibly to acetylcholine receptors embedded in the membrane of the postsynaptic nerve terminal. The binding of ACh to the receptors triggers a nerve impulse in the postsynaptic neuron. Finally AChE, anchored to the membrane of the postsynaptic nerve terminal (Figure 2), hydrolyzes ACh to acetate and choline, resulting in the termination of neurotransmission.		When a nerve impulse reaches the presynaptic nerve terminal of a cholinergic synpase, it stimulates the release of the neurotransmitter, ACh (Figure 1), into the synaptic cleft. ACh diffuses across the cleft to the postsynaptic nerve terminal, where it binds reversibly to acetylcholine receptors embedded in the membrane of the postsynaptic nerve terminal. The binding of ACh to the receptors triggers a nerve impulse in the postsynaptic neuron. Finally AChE, anchored to the membrane of the postsynaptic nerve terminal (Figure 2), hydrolyzes ACh to acetate and choline, resulting in the termination of neurotransmission.

Joel L. Sussman: /* '''Background Information''' */

Joel L. Sussman — Thu, 13 Oct 2011 06:47:47 GMT

'''Background Information'''

←Older revision		Revision as of 06:47, 13 October 2011
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	When a nerve impulse reaches the presynaptic nerve terminal of a cholinergic synpase, it stimulates the release of the neurotransmitter, ACh (Figure 1), into the synaptic cleft. ACh diffuses across the cleft to the postsynaptic nerve terminal, where it binds reversibly to acetylcholine receptors embedded in the membrane of the postsynaptic nerve terminal. The binding of ACh to the receptors triggers a nerve impulse in the postsynaptic neuron. Finally AChE, anchored to the membrane of the postsynaptic nerve terminal (Figure 2), hydrolyzes ACh to acetate and choline, resulting in the termination of neurotransmission.		When a nerve impulse reaches the presynaptic nerve terminal of a cholinergic synpase, it stimulates the release of the neurotransmitter, ACh (Figure 1), into the synaptic cleft. ACh diffuses across the cleft to the postsynaptic nerve terminal, where it binds reversibly to acetylcholine receptors embedded in the membrane of the postsynaptic nerve terminal. The binding of ACh to the receptors triggers a nerve impulse in the postsynaptic neuron. Finally AChE, anchored to the membrane of the postsynaptic nerve terminal (Figure 2), hydrolyzes ACh to acetate and choline, resulting in the termination of neurotransmission.
	[[Image:AChE-Page-ACh_shematic.JPG\|left\|thumb\|alt= Alt text\| Figure 1. Chemical Structure of Acetylcholine \|275px]]		[[Image:AChE-Page-ACh_shematic.JPG\|left\|thumb\|alt= Alt text\| Figure 1. Chemical Structure of Acetylcholine \|275px]]
-

	Inhibition of AChE may result in various outcomes, depending on the physiological context. Toxins such as FAS-II, from the green mamba, a poisonous snake found in East Africa, inhibit AChE and ultimately lead to death. However, controlled inhibition of AChE, in patients with Alzheimer’s disease, by drugs designed for this purpose, alleviates their symptoms, including memory loss and disorientation.		Inhibition of AChE may result in various outcomes, depending on the physiological context. Toxins such as FAS-II, from the green mamba, a poisonous snake found in East Africa, inhibit AChE and ultimately lead to death. However, controlled inhibition of AChE, in patients with Alzheimer’s disease, by drugs designed for this purpose, alleviates their symptoms, including memory loss and disorientation.

Joel L. Sussman: /* '''Background Information''' */

Joel L. Sussman — Thu, 13 Oct 2011 06:46:12 GMT

'''Background Information'''

←Older revision		Revision as of 06:46, 13 October 2011
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	==='''Background Information'''===		==='''Background Information'''===
-
-

	[[Image:AChE-Page-Cholinergic-Synapse.jpg\|thumb\|alt= Alt text\| Figure 2. Cholinergic Synapse \|375px]]		[[Image:AChE-Page-Cholinergic-Synapse.jpg\|thumb\|alt= Alt text\| Figure 2. Cholinergic Synapse \|375px]]


-	When a nerve impulse reaches the presynaptic nerve terminal, ~~where~~ it stimulates the release of the neurotransmitter, ACh (Figure 1), into the ~~cholinergic synapse~~. ACh diffuses across the ~~synapse~~ to the postsynaptic nerve terminal, ~~and~~ binds to receptors embedded in the membrane of the postsynaptic nerve terminal. The binding of ACh to receptors in the postsynaptic neuron ~~re-initiates the nerve impulse~~. Finally AChE, anchored to the membrane of the postsynaptic nerve terminal (Figure 2), hydrolyzes ACh to acetate and choline resulting in the termination of ~~the nerve impulse at the synapse~~.	+	When a nerve impulse reaches the presynaptic nerve terminal of a cholinergic synpase, it stimulates the release of the neurotransmitter, ACh (Figure 1), into the synaptic cleft. ACh diffuses across the cleft to the postsynaptic nerve terminal, where it binds reversibly to acetylcholine receptors embedded in the membrane of the postsynaptic nerve terminal. The binding of ACh to the receptors triggers a nerve impulse in the postsynaptic neuron. Finally AChE, anchored to the membrane of the postsynaptic nerve terminal (Figure 2), hydrolyzes ACh to acetate and choline, resulting in the termination of neurotransmission.
	[[Image:AChE-Page-ACh_shematic.JPG\|left\|thumb\|alt= Alt text\| Figure 1. Chemical Structure of Acetylcholine \|275px]]		[[Image:AChE-Page-ACh_shematic.JPG\|left\|thumb\|alt= Alt text\| Figure 1. Chemical Structure of Acetylcholine \|275px]]
-	Inhibition of AChE may result in ~~different~~ outcomes, depending on the physiological context. Toxins such as FAS-II from the ~~East African Green Mamba~~ snake inhibit AChE and ultimately lead to death. ~~Conversely~~, ~~reversible~~ inhibition of AChE, in patients with Alzheimer’s disease, ~~is an effective way to improve~~ their symptoms, including memory loss and disorientation.	+
		+
		+	Inhibition of AChE may result in various outcomes, depending on the physiological context. Toxins such as FAS-II, from the green mamba, a poisonous snake found in East Africa, inhibit AChE and ultimately lead to death. However, controlled inhibition of AChE, in patients with Alzheimer’s disease, by drugs designed for this purpose, alleviates their symptoms, including memory loss and disorientation.

	{{clear}}		{{clear}}

Joel L. Sussman: /* '''Introduction''' */

Joel L. Sussman — Thu, 13 Oct 2011 06:42:43 GMT

'''Introduction'''

←Older revision		Revision as of 06:42, 13 October 2011
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	==='''Introduction'''===		==='''Introduction'''===

-	Acetylcholinesterase(AChE) is essential for hydrolysis of the neurotransmitter acetylcholine (ACh), and, therefore, for termination of impulse transmission at cholinergic synapses (Figure 2). Irreversible inhibition of AChE can result in accumulation of ACh at cholinergic synapses and, ultimately, to death. Conversely, decreased levels of ACh may result in the memory deficits associated with Alzheimer's disease <ref>PMID: 14501022</ref>. AChE has a deep (20Å) and narrow (5Å) gorge lined with 14 aromatic residues, with its active site located near the bottom of the gorge<ref>PMID: 1678899</ref>. Initially, ACh binds to the peripheral anionic site (PAS) of AChE, and is funneled down the gorge to the active site by interactions between its quaternary ammonium group and the aromatic rings of 14 aromatic amino acid residues lining the gorge. At the active site, ACh is oriented for hydrolysis by interactions between the catalytic anionic site and its quaternary ammonium group. Fasciculin-II (FAS-II), a potent polypeptide toxin present in the venom of the East African green mamba (Dendroaspis angusticeps), inhibits AChE by binding to the top of the active-site gorge, interacting tightly with residues that form the PAS; it thus prevents ACh from entering the active-site gorge<ref>PMID:8747462</ref>. The Hostos-Lincoln Academy Students Modeling A Research Topic (S.M.A.R.T) team and the Center for BioMolecular Modeling have designed and fabricated two physical models using a combination of computational molecular modeling and three-dimensional (3D) printing technology: ''Torpedo californica'' (''Tc'') AChE complexed with a modeled ACh molecule ligand, and a complex of FAS-II with ''Tc''AChE.	+	Acetylcholinesterase(AChE) is essential for hydrolysis of the neurotransmitter acetylcholine (ACh), and, therefore, for termination of impulse transmission at cholinergic synapses (Figure 2). Irreversible inhibition of AChE can result in accumulation of ACh at cholinergic synapses and, ultimately, to death. Conversely, decreased levels of ACh may result in the memory deficits associated with Alzheimer's disease<ref>PMID: 14501022</ref>. AChE has a deep (20Å) and narrow (5Å) gorge lined with 14 aromatic residues, with its active site located near the bottom of the gorge<ref>PMID: 1678899</ref>. Initially, ACh binds to the peripheral anionic site (PAS) of AChE, and is funneled down the gorge to the active site by interactions between its quaternary ammonium group and the aromatic rings of 14 aromatic amino acid residues lining the gorge. At the active site, ACh is oriented for hydrolysis by interactions between the catalytic anionic site and its quaternary ammonium group. Fasciculin-II (FAS-II), a potent polypeptide toxin present in the venom of the East African green mamba (Dendroaspis angusticeps), inhibits AChE by binding to the top of the active-site gorge, interacting tightly with residues that form the PAS; it thus prevents ACh from entering the active-site gorge<ref>PMID:8747462</ref>. The Hostos-Lincoln Academy Students Modeling A Research Topic (S.M.A.R.T) team and the Center for BioMolecular Modeling have designed and fabricated two physical models using a combination of computational molecular modeling and three-dimensional (3D) printing technology: ''Torpedo californica'' (''Tc'') AChE complexed with a modeled ACh molecule ligand, and a complex of FAS-II with ''Tc''AChE.

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Joel L. Sussman: /* '''Acetylcholinesterase: A Story of Substrate Traffic and Inhibition''' */

Joel L. Sussman — Thu, 13 Oct 2011 06:39:57 GMT

'''Acetylcholinesterase: A Story of Substrate Traffic and Inhibition'''

←Older revision		Revision as of 06:39, 13 October 2011
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	==='''Introduction'''===		==='''Introduction'''===

-	Acetylcholinesterase(AChE) is essential for hydrolysis of the neurotransmitter acetylcholine (ACh), and, therefore, for termination of impulse transmission at cholinergic synapses (Figure 2). Irreversible inhibition of AChE can result in accumulation of ACh at cholinergic synapses and, ultimately, to death. Conversely, decreased levels of ACh may result in the memory deficits associated with Alzheimer's disease <ref>PMID: 14501022</ref>. AChE has a deep (20Å) and narrow (5Å) gorge lined with 14 aromatic residues, with its active site located near the bottom of the gorge<ref>PMID: 1678899</ref>. Initially, ACh binds to the peripheral anionic site (PAS) of AChE, and is funneled down the gorge to the active site by interactions between its quaternary ammonium group and the aromatic rings of 14 aromatic amino acid residues lining the gorge. At the active site, ACh is oriented for hydrolysis by interactions between the catalytic anionic site and its quaternary ammonium group. Fasciculin-II (FAS-II), a potent polypeptide toxin present in the venom of the East African green mamba (Dendroaspis angusticeps), inhibits AChE by binding to the top of the active-site gorge, interacting tightly with residues that form the PAS; it thus prevents ACh from entering the active-site gorge<ref>PMID:8747462</ref>. The Hostos-Lincoln Academy Students Modeling A Research Topic (S.M.A.R.T) team and the Center for BioMolecular Modeling have designed and fabricated two physical models using a combination of computational molecular modeling and three-dimensional (3D) printing technology: "Torpedo californica" ("Tc") AChE complexed with a modeled ACh molecule ligand, and a complex of FAS-II with "Tc"AChE.	+	Acetylcholinesterase(AChE) is essential for hydrolysis of the neurotransmitter acetylcholine (ACh), and, therefore, for termination of impulse transmission at cholinergic synapses (Figure 2). Irreversible inhibition of AChE can result in accumulation of ACh at cholinergic synapses and, ultimately, to death. Conversely, decreased levels of ACh may result in the memory deficits associated with Alzheimer's disease <ref>PMID: 14501022</ref>. AChE has a deep (20Å) and narrow (5Å) gorge lined with 14 aromatic residues, with its active site located near the bottom of the gorge<ref>PMID: 1678899</ref>. Initially, ACh binds to the peripheral anionic site (PAS) of AChE, and is funneled down the gorge to the active site by interactions between its quaternary ammonium group and the aromatic rings of 14 aromatic amino acid residues lining the gorge. At the active site, ACh is oriented for hydrolysis by interactions between the catalytic anionic site and its quaternary ammonium group. Fasciculin-II (FAS-II), a potent polypeptide toxin present in the venom of the East African green mamba (Dendroaspis angusticeps), inhibits AChE by binding to the top of the active-site gorge, interacting tightly with residues that form the PAS; it thus prevents ACh from entering the active-site gorge<ref>PMID:8747462</ref>. The Hostos-Lincoln Academy Students Modeling A Research Topic (S.M.A.R.T) team and the Center for BioMolecular Modeling have designed and fabricated two physical models using a combination of computational molecular modeling and three-dimensional (3D) printing technology: ''Torpedo californica'' (''Tc'') AChE complexed with a modeled ACh molecule ligand, and a complex of FAS-II with ''Tc''AChE.

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Joel L. Sussman: /* '''Introduction''' */

Joel L. Sussman — Thu, 13 Oct 2011 06:36:51 GMT

'''Introduction'''

←Older revision		Revision as of 06:36, 13 October 2011
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	==='''Introduction'''===		==='''Introduction'''===

-	Acetylcholinesterase(AChE) is essential for ~~the~~ hydrolysis of the neurotransmitter acetylcholine (ACh), and therefore ~~the~~ termination of ~~the nerve~~ impulse in cholinergic synapses (Figure 2). Irreversible inhibition of AChE can ~~lead to increased levels~~ of ACh in cholinergic synapses and ultimately death. Conversely, ~~suppressed~~ levels of ACh may ~~lead to~~ memory deficits associated with Alzheimer's disease <ref>PMID: 14501022</ref>. AChE has a deep (20Å) and narrow (5Å) gorge lined with 14 aromatic residues, with its active site at the bottom of the gorge<ref>PMID: 1678899</ref>. Initially, ACh binds to the peripheral anionic site(PAS) of AChE and is funneled down the gorge to the active site by interactions between the aromatic rings of ~~the~~ 14 aromatic residues ~~and~~ the ~~quaternary ammonium ion of ACh~~. At the active site, ACh is oriented for hydrolysis by interactions between the catalytic anionic ~~ion~~ site and ~~the~~ quaternary ammonium ~~ion of ACh~~. ~~The~~ Fasciculin-II (FAS-II)~~toxin~~, a ~~component~~ of the East African ~~Green Mamba snake~~(''Dendroaspis angusticeps'') ~~venom~~, inhibits AChE by binding to the top of the active-site gorge, ~~including~~ residues that form the PAS; thus ~~preventing~~ ACh from entering the active-site gorge<ref>PMID:8747462</ref>. The Hostos-Lincoln Academy Students Modeling A Research Topic (S.M.A.R.T) team and the Center for BioMolecular Modeling have designed and fabricated two physical models using a combination of computational molecular modeling and three-dimensional(3D) printing technology: ''Torpedo californica'' (''Tc'') AChE ~~in complex~~ with a modeled ACh ligand and ~~''Tc''AChE in~~ complex ~~with~~ FAS-II.	+	Acetylcholinesterase(AChE) is essential for hydrolysis of the neurotransmitter acetylcholine (ACh), and, therefore, for termination of impulse transmission at cholinergic synapses (Figure 2). Irreversible inhibition of AChE can result in accumulation of ACh at cholinergic synapses and, ultimately, to death. Conversely, decreased levels of ACh may result in the memory deficits associated with Alzheimer's disease <ref>PMID: 14501022</ref>. AChE has a deep (20Å) and narrow (5Å) gorge lined with 14 aromatic residues, with its active site located near the bottom of the gorge<ref>PMID: 1678899</ref>. Initially, ACh binds to the peripheral anionic site (PAS) of AChE, and is funneled down the gorge to the active site by interactions between its quaternary ammonium group and the aromatic rings of 14 aromatic amino acid residues lining the gorge. At the active site, ACh is oriented for hydrolysis by interactions between the catalytic anionic site and its quaternary ammonium group. Fasciculin-II (FAS-II), a potent polypeptide toxin present in the venom of the East African green mamba (Dendroaspis angusticeps), inhibits AChE by binding to the top of the active-site gorge, interacting tightly with residues that form the PAS; it thus prevents ACh from entering the active-site gorge<ref>PMID:8747462</ref>. The Hostos-Lincoln Academy Students Modeling A Research Topic (S.M.A.R.T) team and the Center for BioMolecular Modeling have designed and fabricated two physical models using a combination of computational molecular modeling and three-dimensional (3D) printing technology: "Torpedo californica" ("Tc") AChE complexed with a modeled ACh molecule ligand, and a complex of FAS-II with "Tc"AChE.
		+
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Allison Granberry at 00:42, 12 October 2011

Allison Granberry — Wed, 12 Oct 2011 00:42:49 GMT

←Older revision		Revision as of 00:42, 12 October 2011
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-	=='''~~Physical Models of~~ Acetylcholinesterase ~~in Complex with Acetylcholine~~ and ~~the Green Mamba Snake Toxin, Fasciculin-II~~'''==	+	=='''Acetylcholinesterase: A Story of Substrate Traffic and Inhibition'''==
	Students: Mary Acheampong. Daviana Dueño, Bobby Glover, Alafia Henry, Randol Mata, and Marisa VanBrakle, Hostos-Lincoln Academy.		Students: Mary Acheampong. Daviana Dueño, Bobby Glover, Alafia Henry, Randol Mata, and Marisa VanBrakle, Hostos-Lincoln Academy.

Allison Granberry at 20:15, 9 October 2011

Allison Granberry — Sun, 09 Oct 2011 20:15:55 GMT

←Older revision		Revision as of 20:15, 9 October 2011
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-	[[Image:AChE-Page-Cholinergic-Synapse.jpg\|thumb\|alt= Alt text\| Figure 2. ~~Cholernergic~~ Synapse \|375px]]	+	[[Image:AChE-Page-Cholinergic-Synapse.jpg\|thumb\|alt= Alt text\| Figure 2. Cholinergic Synapse \|375px]]

Joel L. Sussman: /* '''Background Information''' */

Joel L. Sussman — Sun, 09 Oct 2011 19:40:23 GMT

'''Background Information'''

←Older revision		Revision as of 19:40, 9 October 2011
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-	When a nerve impulse reaches the presynaptic nerve terminal, where it stimulates the release of the neurotransmitter, ACh (Figure 1), into the cholinergic synapse. ACh diffuses across the synapse to the postsynaptic nerve terminal, and binds to receptors embedded in the membrane of the postsynaptic nerve terminal. The binding of ACh to receptors in the postsynaptic neuron re-initiates the nerve impulse. Finally AChE, anchored to the membrane of the postsynaptic nerve terminal(Figure 2), hydrolyzes ACh to acetate and choline resulting in the termination of the nerve impulse at the synapse.	+	When a nerve impulse reaches the presynaptic nerve terminal, where it stimulates the release of the neurotransmitter, ACh (Figure 1), into the cholinergic synapse. ACh diffuses across the synapse to the postsynaptic nerve terminal, and binds to receptors embedded in the membrane of the postsynaptic nerve terminal. The binding of ACh to receptors in the postsynaptic neuron re-initiates the nerve impulse. Finally AChE, anchored to the membrane of the postsynaptic nerve terminal (Figure 2), hydrolyzes ACh to acetate and choline resulting in the termination of the nerve impulse at the synapse.
	[[Image:AChE-Page-ACh_shematic.JPG\|left\|thumb\|alt= Alt text\| Figure 1. Chemical Structure of Acetylcholine \|275px]]		[[Image:AChE-Page-ACh_shematic.JPG\|left\|thumb\|alt= Alt text\| Figure 1. Chemical Structure of Acetylcholine \|275px]]
	Inhibition of AChE may result in different outcomes, depending on the physiological context. Toxins such as FAS-II from the East African Green Mamba snake inhibit AChE and ultimately lead to death. Conversely, reversible inhibition of AChE, in patients with Alzheimer’s disease, is an effective way to improve their symptoms, including memory loss and disorientation.		Inhibition of AChE may result in different outcomes, depending on the physiological context. Toxins such as FAS-II from the East African Green Mamba snake inhibit AChE and ultimately lead to death. Conversely, reversible inhibition of AChE, in patients with Alzheimer’s disease, is an effective way to improve their symptoms, including memory loss and disorientation.