Ferredoxin: Difference between revisions

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[[Image:small_wh_ray0001.gif|left|150px]]<br />

~~'''3D structure of acetylcholinesterase'''<br />~~

Ferredoxin (Fd) is found in chloroplasts which mediates electron transfer and contains an iron-sulfur cluster. It is involved in the photosynthesis process where its iron atoms accept or discharge electrons when they are being oxidized or reduced. The iron-sulfur cluster can contain 2Fe-2S and is termed plant-like or 3Fe-4S or 4Fe-4S clusters.

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'''Acetylcholinesterase''' (AChE) is key enzyme in the nervous system of animals. By rapid hydrolysis of the neurotransmitter, '''acetylcholine''' (ACh), AChE terminates neurotransmission at cholinergic synapses. It is a very fast enzyme, especially for a serine hydrolase, functioning at a rate approaching that of a diffusion-controlled reaction. AChE inhibitors are among the key drugs approved by the FDA for management of Alzheimer's disease (AD). The powerful toxicity of organophosphorus (OP) poisons is attributed primarily to their potent AChE inhibitors.

[[Image:Synapse_Schematic.jpg|thumb|Cholinergic Synapse|300px|left]]

The 3D structure of ''Torpedo californica'' AChE (''Tc''AChE) ([http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1678899 Sussman et al. & Silman (1991)]) opened up new horizons in research on an enzyme that had already been the subject of intensive investigation. The unanticipated structure of this extremely rapid enzyme, in which the active site was found to be buried at the bottom of a

~~<scene name='Acetylcholinesterase/New_down_gorge/2'>deep and narrow gorge</scene>,~~

~~lined by aromatic residues, led to a revision of the views then held concerning substrate traffic, recognition,~~

and hydrolysis ([http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10545346 Botti et al. Sussman & Silman (1999)]). To understand how those aromatic residues behave with the enzyme, see [[Flexibility of aromatic residues in acetylcholinesterase]].

Alzheimer’s disease (AD) is a debilitating brain disease that occurs in around 10% of the elderly and, as yet, there is no known cure. At present, the most widely used treatments consist are medications that attempt to increase the brain’s levels of ACh, whose levels decrease with onset of disease. These drugs work by interfering with AChE. Thus drugs that are mild inhibitors of AChE, like Tacrine, E2020 (Aricept) and the Traditonal Chinese Medicine (TCM) Huperzine appear to retard symptoms of AD.

~~<applet load='1ea5_rot.pdb' size='300' color='white' frame='true' spin='on' caption='AChE' align='right' script='Acetylcholinesterase/New_down_gorge/5'~~

~~'''3D structure of acetylcholinesterase'''<br />~~

The active site gorge has <scene name='Acetylcholinesterase/New_down_gorge/6'>two binding sites</scene>, a catalytic site (consisting of the catalytic triad together with Trp84 & Phe330) and a peripheral site (including Trp 279 & Tyr 121), which helps prebind the substrate and direct it toward the active site. The 3D structure showed not only that the active site was buried deep in the enzyme, but surprisingly, there were no negatively charged residues along this gorge, as was expected to help attract the positively charged ACh substrate, rather, instead, a series of aromatic residues that are highly conserved in all AChE sequences. See: [[AChE inhibitors and substrates]]

Ferredoxin: Difference between revisions

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@@ Line 1: / Line 1: @@
 [[Image:small_wh_ray0001.gif|left|150px]]<br />
 <applet load="1ea5_rot.pdb" size="300" color="white" frame="true" spin="on" caption="AChE" align="right" script="Acetylcholinesterase/New_down_gorge/1" />
-'''3D structure of acetylcholinesterase'''<br />
 Ferredoxin (Fd) is found in chloroplasts which mediates electron transfer and contains an iron-sulfur cluster.  It is involved in the photosynthesis process where its iron atoms accept or discharge electrons when they are being oxidized or reduced.  The iron-sulfur cluster can contain 2Fe-2S and is termed plant-like or 3Fe-4S or 4Fe-4S clusters.
@@ Line 100: / Line 100: @@
 '''Acetylcholinesterase''' (AChE) is key enzyme in the nervous system of animals. By rapid hydrolysis of the neurotransmitter, '''acetylcholine''' (ACh), AChE terminates neurotransmission at cholinergic synapses. It is a very fast enzyme, especially for a serine hydrolase, functioning at a rate approaching that of a diffusion-controlled reaction. AChE inhibitors are among the key drugs approved by the FDA for management of Alzheimer's disease (AD). The powerful toxicity of organophosphorus (OP) poisons is attributed primarily to their potent AChE inhibitors.
 [[Image:Synapse_Schematic.jpg|thumb|Cholinergic Synapse|300px|left]]
-The 3D structure of ''Torpedo californica'' AChE (''Tc''AChE) ([http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1678899 Sussman et al. & Silman (1991)]) opened up new horizons in research on an enzyme that had already been the subject of intensive investigation. The unanticipated structure of this extremely rapid enzyme, in which the active site was found to be buried at the bottom of a
-<scene name='Acetylcholinesterase/New_down_gorge/2'>deep and narrow gorge</scene>,
-lined by aromatic residues, led to a revision of the views then held concerning substrate traffic, recognition,
-and hydrolysis ([http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10545346 Botti et al. Sussman & Silman (1999)]). To understand how those aromatic residues behave with the enzyme, see [[Flexibility of aromatic residues in acetylcholinesterase]].
-Alzheimer’s disease (AD) is a debilitating brain disease that occurs in around 10% of the elderly and, as yet, there is no known cure. At present, the most widely used treatments consist are medications that attempt to increase the brain’s levels of ACh, whose levels decrease with onset of disease.  These drugs work by interfering with AChE. Thus drugs that are  mild inhibitors of AChE, like Tacrine, E2020 (Aricept) and the Traditonal Chinese Medicine (TCM) Huperzine appear to retard symptoms of AD.
-<applet load='1ea5_rot.pdb' size='300' color='white' frame='true' spin='on' caption='AChE' align='right' script='Acetylcholinesterase/New_down_gorge/5'
-'''3D structure of acetylcholinesterase'''<br />
-The active site gorge has <scene name='Acetylcholinesterase/New_down_gorge/6'>two binding sites</scene>, a catalytic site (consisting of the catalytic triad together with Trp84 & Phe330) and a peripheral site (including Trp 279 & Tyr 121), which helps prebind the substrate and direct it toward the active site.  The 3D structure showed not only that the active site was  buried deep in the enzyme, but surprisingly, there were no negatively charged residues along this gorge, as was expected to help attract the positively charged ACh substrate, rather, instead, a series of aromatic residues that are highly conserved  in all AChE sequences. See: [[AChE inhibitors and substrates]]