Sandbox11: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 9: | Line 9: | ||
==Introduction== | ==Introduction== | ||
Acetylcholinesterase | Acetylcholinesterase breaks down acetylcholine into acetic acid and choline via a hydrolysis reaction. Acetylcholine is a neurotransmitter that signals muscle contraction. If acetylcholine is not broken down, then the chemical builds up in the synapses between nerve cells and muscle cells resulting in loss of muscle function and ultimately paralysis. The enzyme’s extremely fast reaction rate (approaching the diffusion limit) for breaking one acetylcholine into its two components indicates acetylcholinesterase’s biological importance. Many natural poisons and toxins work by inhibiting this enzyme, thus, paralyzing the victim. | ||
Intentionally inhibiting acetylcholinesterase is a treatment for Alzheimer’s disease. Alzheimer’s is basically the progressive breakdown of the nervous system. Worldwide, there are an estimated 20 million individuals diagnosed with Alzheimer’s, most of whom are over the age of 65. Symptoms of the disease include confusion, irritability and aggressioin, mood swings, language breakdown, long-term memory loss, and eventually loss of bodily functions. To help combat nerve cell degeneration, these acetylcholinesterase inhibitors partially block the enzyme so that excess neurotransmitters remain in the synapse and strengthen the signal. | Intentionally inhibiting acetylcholinesterase is a treatment for Alzheimer’s disease. Alzheimer’s is basically the progressive breakdown of the nervous system. Worldwide, there are an estimated 20 million individuals diagnosed with Alzheimer’s, most of whom are over the age of 65. Symptoms of the disease include confusion, irritability and aggressioin, mood swings, language breakdown, long-term memory loss, and eventually loss of bodily functions. To help combat nerve cell degeneration, these acetylcholinesterase inhibitors partially block the enzyme so that excess neurotransmitters remain in the synapse and strengthen the signal. | ||
| Line 36: | Line 36: | ||
{{STRUCTURE_1acj | PDB=1acj | SCENE= }} | {{STRUCTURE_1acj | PDB=1acj | SCENE= }} | ||
The active site of Torpedo californica acetylcholinesterase (TcAChE) is buried at the bottom of a narrow, deep gorge in the enzyme, and contains a <scene name='Sandbox11/Catalytic_triad/6'>catalytic triad</scene> consisting of Ser200, Glu327, and His440. When complexed with tacrine (THA), the aromatic rings of Trp84 and | The active site of Torpedo californica acetylcholinesterase (TcAChE) is buried at the bottom of a narrow, deep gorge in the enzyme, and contains a <scene name='Sandbox11/Catalytic_triad/6'>catalytic triad</scene> consisting of Ser200, Glu327, and His440. When complexed with tacrine (THA), the aromatic rings of <scene name='Sandbox11/Trp84 and Phe 330/1'>TextToBeDisplayed</scene>sandwich the THA’s acridine ring . The phenyl ring of Phe330 lies parallel to and in contact with THA. THA is stacked against Trp-84. Its ring nitrogen is H-bonded to the main chain carbonyl oxygen of Hist-440 and it’s amino nitrogen is H-bonded to a water molecule. | ||
==Additional Features== | ==Additional Features== | ||
