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| == Disease == | | == Disease == |
| alzeihmers
| | As noted above, AChE is known for the blocking the signal of acetylcholine to the synaptic cleft. It plays important role in neural and muscular functions because it has been linked to neuronal apoptosis. The disease it is mainly known for being attributed to is Alzheimer's. Now it does not specifically cause this disease but it has been used to formulate medications and treatments that are already FDA approved. More so its inhibitor is what is used in the formulation of these treatments. |
| mutations
| | Recall that acetylcholinesterase is also a toxin. In a study in which they were testing the effectiveness on mice the venom itself had the toxin. |
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| == Relevance ==
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| treatment of diseases
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| ===testing===
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| == Structural highlights == | | == Structural highlights == |
| ===Scene 1=== | | ===Scene 1=== |
| this is the <scene name='78/781216/00pink_rib/1'>acetylcholinesterase protein</scene>
| | This is a view of the <scene name='78/781216/00blue_ligands/2'>protein ligands</scene> that are binding to the enzyme. |
| ===Scene 2=== | | ===Scene 2=== |
| this is a view of the <scene name='78/781216/00blue_ligands/2'>protein ligand</scene>
| | These are the <scene name='78/781216/00active_sites/1'>active binding sites</scene>. They are mutated points however the one deepest in a groove is the primary. |
| ===Scene 3=== | | ===Scene 3=== |
| this is a visual of the <scene name='78/781216/00active_sites/1'>active binding sites</scene>
| | This is the view of <scene name='78/781216/12_mutations/1'>mutations</scene> |
| ===Scene 4=== | | ===Scene 4=== |
| This is the veiw of <scene name='78/781216/12_mutations/1'>mutations</scene> | | This is a view of <scene name='78/781216/12_binding_pockets/1'>binding pockets</scene> |
| ===Scene 5===
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| this is a view of <scene name='78/781216/12_binding_pockets/1'>binding pockets</scene>
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| This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. |
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Acetylcholinesterase
| Human acetylcholinesterase (AChE) is an enzyme which inhibits the function acetylcholine by way of a rapid hydrolysis. It is classified as a toxin/ hydrolase and has been linked to things such as snake venom and has been used in the the development of treatment for diseases which involve the nervous system and the transmission of signals to muscles. This specific enzyme has 3 active binding sites and 6 mutations. Each of which either causing a loss of activity or a mis-folding.
You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.
Function
Acetylcholinesterase functions primarily in the synaptic cleft to stop the signal to the neurotransmitter. This is done by way of a rapid hydrolysis reaction of acetylcholine yielding the products acetate, choline and a hydrogen ion. In conjunction with its biological function it has an unusually high catalytic activity because considering the fact that it is a serine hydrolase it functions more closely to the rate of a limitation by diffusion control. [1] A big contributer to the activity of the enzyme is the mutagenesis. The mutations noted are at positions 234, 365, and 478, these are all also the active sites of the enzyme. One happens at the acyl ester intermediate, while the other two are at a sort of charge relay system. The one located in the acyl ester intermediate functions as the main active site. It is located deep in the gorge lined largely by aromatic residues along with many Serines and this specific sites mutation causes a loss in activity.
Another structure that contributes greatly to the function of the protein is the ligand binding and interactions of the molecule. It is important to note that there is a high binding affinity for ligands to the structure. This in turn is what increases the enzymes catalytic rate.
Disease
As noted above, AChE is known for the blocking the signal of acetylcholine to the synaptic cleft. It plays important role in neural and muscular functions because it has been linked to neuronal apoptosis. The disease it is mainly known for being attributed to is Alzheimer's. Now it does not specifically cause this disease but it has been used to formulate medications and treatments that are already FDA approved. More so its inhibitor is what is used in the formulation of these treatments.
Recall that acetylcholinesterase is also a toxin. In a study in which they were testing the effectiveness on mice the venom itself had the toxin.
Structural highlights
Scene 1
This is a view of the protein ligands that are binding to the enzyme.
Scene 2
These are the active binding sites. They are mutated points however the one deepest in a groove is the primary.
Scene 3
This is the view of mutations
Scene 4
This is a view of binding pockets
This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:https://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
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References
1. Harel M, Kleywegt GJ, Ravelli RB, Silman I, Sussman JL. Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target. Structure. 1995 Dec 15;3(12):1355-66. doi: 10.1016/s0969-2126(01)00273-8. PMID: 8747462.
2. Dvir, H., Silman, I., Harel, M., Rosenberry, T. L., & Sussman, J. L. (2010). Acetylcholinesterase: from 3D structure to function. Chemico-biological interactions, 187(1-3), 10–22. https://doi.org/10.1016/j.cbi.2010.01.042
3. Shafferman, A., Kronman, C., Flashner, Y., Leitner, M., Grosfeld, H., Ordentlich, A., Gozes, Y., Cohen, S., Ariel, N., & Barak, D. (1992). Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. The Journal of biological chemistry, 267(25), 17640–17648.
