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Generation of DNA nucleotides

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Postby JackBean » Sat Jan 30, 2010 10:36 pm

That doesn't make any sense to reply here, because YOU WILL BE STILL SAYING THE SAME THINGS AND NOT READING THE BOOK!!!
Just read, how enzymes work in common, how they procced through the reaction and stuff
http://www.biolib.cz/en/main/

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Postby kolean » Sun Jan 31, 2010 1:14 am

I think I am getting off this merry-go-round. You need to just read and take it all in. Do not fight it just yet, put it on the back burner. Let it simmer.
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Re: Generation of DNA nucleotides

Postby gs99 » Sat Feb 06, 2010 4:35 pm

I still have not seen an explanation for this statement:

kolean wrote:Water is very polar, and can even form clathrins around certain other charge molecules. It can hold a protein in place with all of its hydrogen bonding.


The book "Biochemistry" by Voet & Voet (1990) refers to clathrin only as a protein.

How can water itself form a protein?

JackBean wrote:as I told you, kolean didn't mean (I guess) the proteins clathrins!!!

What other clathrins are there?
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Postby JackBean » Sat Feb 06, 2010 5:17 pm

I knew, I should lock it here.

I told you already, instead of clathrin, put into the sentence cluster.
http://www.biolib.cz/en/main/

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Re: Generation of DNA nucleotides

Postby gs99 » Sat Feb 06, 2010 6:21 pm

Yes, you did mention that.
But I didn't find anything substantial about water "clusters".
Not mentioned in the book by Voet.

http://en.wikipedia.org/wiki/Water_cluster
says: "So little is understood about water clusters in bulk water that it is considered one of the unsolved problems in chemistry."

But we're to accept that water forms "clusters" at the right time to move molecules into DNA pol.

Aren't you curious as to how that happens?

And without a reply from kolean, we really don't know what was meant, do we? Is it possible that kolean knows something that you don't?
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Postby JackBean » Sat Feb 06, 2010 6:32 pm

for sure she knows something I don't :lol:

look for hydration sheath. That are water molecules, which surround every dissolved molecule
http://www.biolib.cz/en/main/

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Re: Generation of DNA nucleotides

Postby jonmoulton » Tue Feb 09, 2010 4:15 pm

Clathrate. Specifically, water clathrate.

I hope this helps with the (water cluster)(hydration sheath)(clathrin) discussion. Clathrin is a protein that forms an ordered structure around invaginating membranes during some forms of endocytosis, in a manner analogous to a clathrate. A clathrate is a geometrically ordered, hydrogen-bonded cage of water surrounding an insoluble substance immersed in water.

Argument for clathrate formation at hydrophobic biomolecular surfaces:
http://www.pnas.org/content/92/18/8308.abstract
http://www.pnas.org/content/92/18/8308.full.pdf

Argument against clathrate formation at hydrophobic biomolecular surfaces:
http://ww2.chemistry.gatech.edu/~lw26/b ... LDW_30.pdf

This doesn't address water, but the idea is similar: http://en.wikipedia.org/wiki/Clathrate

Nice discussion in the context of biomolecules:
http://www.i-sis.org.uk/TIOCW.php

Here is older work describing stable water clathrates: http://www.jstor.org/pss/100444
Note that the water clathrates that are thought to blanket hydrophobic regions of biomolecules are not as stable as those described in this paper.

You can chill a mixture and make the clathrate more stable: http://bit.ly/9ds6AT

Nice pictures. I doubt such complete complexes could form stably at room temperature, but this shows the extreme case of hypothetical orderliness in a water clathrate. http://www.btinternet.com/~martin.chapl ... hrate.html

This describes gas hydrates instead of water ordered around biomolecules:
http://chem.ps.uci.edu/~kcjanda/Group/g ... cture.html

That's as far as I'm ready to go now. Best wishes stalking reality!
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Re: Generation of DNA nucleotides

Postby gs99 » Wed Feb 10, 2010 2:59 pm

Thanks jonmoulton for that clarifying information and references.
jonmoulton wrote:A clathrate is a geometrically ordered, hydrogen-bonded cage of water surrounding an insoluble substance immersed in water.

Still not sure what kolean had in mind.

My basic interest has been the rapid motion of the nucleotides toward their parking space in the DNA pol.

Could water clathrates play a part in this?
Since they seem to be closed "structures", my initial guess is no.
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Re: Generation of DNA nucleotides

Postby jonmoulton » Wed Feb 10, 2010 4:27 pm

I don't see a mechanism by which clathrates would speed the motion of nucleotides toward the polymerase active site.

There are several factors which might increase the rate of nucleotide triphosphate (NTP) entry into the active site beyond the rate predicted from simple diffusion. For these, I am speculating. The polymerase itself might have sites on its surface with some affinity to NTPs, allowing the NTPs to "queue up" by the active site. I am also thinking of the interaction of Dicer and Argonaute, where Dicer associates with Argonaute and loads a newly-matured miRNA strands directly into Argonaute's RNA binding domain -- perhaps there is another protein that catches NTPs and loads them onto polymerase. There is lots of higher-order structure in cells that is just being explored, regions of protein interaction that lead to non-average composition; I expect these regions of local order are the rule rather than the exception. Perhaps there are yet-to-be described interactions between NPTs and cellular components that tend to concentrate NTPs near a polymerase, increasing the rate of productive collision between NTPs and polymerase by increasing the local concentration of NTPs.

However, none of these potential mechanisms need to pre-sort the NTPs so that the complementary nucleotide is always the next loaded onto the polymerase. The cell doesn't need to get the correct nucleotide for pairing, it just needs a steady supply of ATP, CTP, GTP and TTP; the Watson-Crick pairing that occurs (or, 3/4 of the time, doesn't occur) at the site of strand elongation is sufficient to elongate the strand rapidly and fairly accurately (and with the polymerases proofreading activity, the accuracy is increased). Get ALL the nucleotide triphosphates to the polymerase and let the polymerase and template strand sort them out.
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Re: Generation of DNA nucleotides

Postby gs99 » Wed Feb 10, 2010 6:27 pm

jonmoulton wrote:Get ALL the nucleotide triphosphates to the polymerase and let the polymerase and template strand sort them out.

Sounds like a plan!

Thanks for all the replies by everybody. It's been very informative and interesting.
Lots more to learn.

One day we might have a microsope that will show all this in living color,
and we'll play it in slow motion.
Details at 11.
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Postby JackBean » Wed Feb 10, 2010 9:19 pm

hardly as we are limited by the wavelength. Maybe NMR...
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Re: Generation of DNA nucleotides

Postby gs99 » Thu Feb 11, 2010 6:43 pm

When glass was discovered 2000 years ago, it paved a way to the common microscope.

When Alexander Bell made the first telephone, he probably didn't envision the sound wave being digitized. Yet the sounds we make on the phone are broken up into tiny parts and then reassembled, enabling many conversations on one wire. Motion pictures are digitized.

I have confidence that someone will discover a similar process with light waves, to provide a "fractionated" light wave or whatever to resolve current microscope restrictions.

Then we'll see "what's happening".
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