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RE: neurotoxin
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by Jaffo on May 23, 2001
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Sasquach should know.
If not, Tim Fried will have it. Or Bryan Fry.
I don't know-- can you tell?
Jaffo
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RE: neurotoxin
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by TIMFRIEDE on May 23, 2001
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Holy smokes that a good question. My knees are shackin man, but I'll give it the old college try. Start takin notes Bigfoot, here's how ya do it. Let's start with these 2 words> neuron and neurotoxin. I will focus on these areas, then bring it all together into one picture, in my own words. The neuron that comes into play is the motor neuron, which is in the peripheral division of the NS, which branches off into the somatic and automonic divisions. This is why I like to call them "periphery neurotoxins", because our focus is on the NMJ, where neuron meets the muscle cell. In the CNS neuron meets neuron to form the pre. and postsynaptic sites of interaction. This does not come into play with snakebite because even the smallest peptide cannot cross the BBB. But, when injected, the effects are dramatic. This is somewhat of a mystery because there are gaps in this barrier. Now, lets forget that and jump to the MN. At the muscle the axon ramifies into branches and the branches form swellings, lets call that the presynaptic side of the nerve terminal. These boutons lie over the end plate and are separated by a cleft(synaptic cleft,about 100nm). There's receptors on the other side that receive neurotransmitters. The nerve terminal makes ACh, which is the transmitter that we will focus on(there are others). The impulse travels down the axon, which creates an Ca influx, along with Na and creates what's called exocytosis, and ACh is released into the cleft. There's also a K efflux which creates a repolariztion(these are the dendrotoxins). ACh then binds to the nAChR and the channels open. There's also muscarinic receptors and the mamba complex comes into play with this also. In a nutshell, that's that. Now, how do the neuro's come into play on this molecular level. It's all a matter of the amino acid seq., which determines the target site of that protein. They need to fit into a receptor site, it's protein vs protein interaction. Here's where the neuro's want to be and have to be, in order to do the damage. The beta's(PLA2's and K-blockers), hit the nerve terminal and do their damage here. One's a enzyme(PLA2,3 divisions) and the other is not(dendrotoxin). The fasciculins attack AChesterase, so I'll lable them as a cleft toxin (BGF), but it could also be a alpha(lol) because the basement membrane favors that side. Then the alpha's, the short and the long, and they bind to the muscle side and fit into the 5-sub-unit nicotinic rec., which blocks ACh from binding. So, I classify the neuro's into these three areas, or periphery toxins. Certain toxins are hydrophilic and certain ones are more hydrophilic, then there's the secondary structures(b-sheets, a-helix),tertiary and quaternary structures, blah, blah. It's way more involved then this, but that's the jist. If I missed anything, or you want to talk more, feel free. Thank-you for the question. This is off the cuff and all mistakes are Jaffo's fault. Tired Tim.
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RE: neurotoxin
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by choco on May 23, 2001
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thank you so much for the imput. i was thinking in the right direction but i was way off. do you recomend any books that i could read for further study? thanks again
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RE: neurotoxin
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by TIMFRIEDE on May 24, 2001
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You bet man. The class I took in college was based of neural science(Eric Kandel and Schwartz). Plus, get Dr.Harvey's book on venom, editor of Toxicon. It ain't about venom, it's about what venom does. Then, venom can be understood. It's not what it is, it's what it does. Then, e-mail the master himself, BGF, the genius himself, the legend of venom. Timbo.
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RE: neurotoxin
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by TIMFRIEDE on May 25, 2001
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He runs the International Venom Database, great site, you'll have to look it up. B has been busy lately, so give him time on a response. It's hooked up with Kingsnake.com, you can find it there. Hey, take some biochem. bro, it opens the windows on protein(venom). Plus, jump over to PubMed and order those doc's through your lib. Toxicon is a great source also, B will hook you up. Tim
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