Talk:Deamidation

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This article does not describe deamidation, it describes isoaspartyl formation. Though formation of isoaspartate does result in deamidation of asparagine residues, "deamidation" is not a correct title this degradation mechanism. This article should be referenced as "Isoaspartate". User:Danielbates 21:22, 15 August 2006 (UTC)

Update 8/15/06: I have created an article entitled Isoaspartate to present this information in a more correct fashion. An article on basic deamidation reactions would be helpful. User:Danielbates 21:35, 15 August 2006 (UTC)

Hi Dan,

Unfortunately, that is incorrect. If you examine the reaction picture, you will see that an asparagine can de-amidate to form aspartate, as well as isoaspartate. In the context of protein chemistry, "deamidation" refers only to the reaction Asn → Asp, which is a common mechanism of protein degradation, one that likely limits the lifetime of proteins in vivo. It is also a problem for purified proteins in vitro, particularly at high pH and temperatures. However, I'm sure that there are other deamidation reactions in organic chemistry. Perhaps we can find a compromise? Isoaspartate formation is clearly not the whole story, but how about renaming it "Deamidation (protein)"? Or perhaps more generally, "Deamidation (peptide)"? Willow 23:22, 15 August 2006 (UTC)

P.S. It's asparagine that's deamidated, not arginine; arginine has a guanidyl group, instead of an amide group. I fixed it at isoaspartate.

P.P.S. A reference for "deamidation of Asn" is TE Creighton Proteins, 2nd. ed., WH Freeman, 1993, pp. 9-10. Willow 23:42, 15 August 2006 (UTC)

Of all the possible titles, isoaspartate seems like definitely the wrong one. That should be an article on, well, isoaspartate. IMO it should stay at deamidation at least for now - obviously there are other deamidation reactions in organic compounds but the basic mechanism is always the same; no reason it can't be illustrated with biomolecules. Unless anyone knows of a very significant/notable/etc deamidation reaction or synthesis step that deserves its own article separate from the biochemical material? I don't, but there's a reason I'm not an organic chemist :)

Also, Willow's image is nice but could be improved with some arrows, which might make it clearer what the reaction is doing and why isoaspartate isn't the only relevant molecule. Opabinia regalis 02:01, 16 August 2006 (UTC)

It's totally true. I think when I made the reaction picture, I didn't know how to make straight reaction arrows and was trying to make up for it in the text. <embarrassed blush> I'll try to fix it soon. I might try to look up other deamidation reactions as well. If we're agreed (Dan?), I'll restore "Deamidation" and spruce up "Isoaspartate" as well. Willow 14:49, 16 August 2006 (UTC)

Sorry, mistyped arginine instead of asparagine. Willow, the fact remains that there are many reactions where deamidation (loss of an amide group) occurs. Deamidation of asparigine residues can happen either by isoapartate formation (as seen in your example) but also there is the spontaneous electrophilic attack of water or a hydroxide ion on the side-chain carboxyl group, followed by the elimination of ammonia and the formation of aspartate. What you have described is NOT deamidation, but is an example of an deamidation reaction. The article needs to be revised to indicate that the term applies to a family of reactions, not one reaction in particular. As well, the deamidation of glutamine to glutamic acid need to be taken into account.

As an aside, are you(Willow) or anyone reading these articles interested in establishing a collection of articles pretaining to protein modifications, both post translational modifications in vivo, as well as possible modifications in solution. I know there is a need for this information, in a consice form, in the protein therpeutics community.--Danielbates 21:40, 23 August 2006 (UTC)

Did a minor rewrite to emphasize the generality of the reaction somewhat. I think a clarification of the image so that the text spends less time trying to reference the steps in the reaction would help to clarify that this is one among multiple possible examples that follow essentially the same mechanism.

The Template:Protein primary structure that Willow has worked on gives a good outline of posttranslational modifications, and there's several red links in it that could use filling in if you're interested. Or feel free to expand the template with any important modifications that have been missed. It is worth making a clear distinction between natural modifications ('desirable' or the result of degradation processes) and laboratory modifications. Opabinia regalis 00:19, 24 August 2006 (UTC)

The re-write is excellent! Re-reading the original text reminds me how cringe-worthy and stubby it was; I'll try to track down my kinetics papers at long last. I think that glutamine does not undergo this deamidation reaction, at least not significantly, because it's much less likely to attack the next peptide group to form the succinimide intermediate. Glutamate does, however, attack the preceding N-terminal amine group in pyroglutamate formation, so there's probably more to this story.

I did make a labeled image with arrows a few days ago and, like a good Wikipedian, uploaded it to the Commons, instead of Wikipedia proper. Foolishly, though, I gave it the same name and now I can't seem to convince the administrators to delete the unlabeled one here. At least, I put it up for deletion four days ago and it's still here — maybe they have a backlog? I'm tempted to just re-upload the labeled image under a new name.

There are several important chemical modification methods but, speaking for myself, I would prefer to keep those separate from the naturally occurring ones on the template. Perhaps a separate template should be made? Right now, I put "chemical modification" as a link on Template:Protein structure determination. To answer your question, Dan, I am interested in contributing to chem. mod.'s and maybe the whole polyketide-synthesis thing as well.

I do agree also that we should cover both the natural and unnatural reactions on individual pages like "Deamidation" and "Methylation". I'll rifle through my orgo books when I get a chance. As an aside, I seem to remember that peptide groups are generally unreactive, owing to their resonance stabilization, and therefore might not deamidate easily even in the presence of water or hydroxide ion. Willow 09:39, 24 August 2006 (UTC)

Willow my coment was directed toward the side chain amide group not the peptide group of Asn and Gln residues. Also great edit, I think we are moving in the right direction.--Danielbates 21:40, 24 August 2006 (UTC)

Willow, have you tried {{db-author}}? The speedy category is probably speedier than the moved-to-commons queue.

It was my understanding that glutamine also does this reaction but at a slower rate. I didn't specify because I don't have a reference for that, so maybe I'm misremembering. Opabinia regalis 04:39, 25 August 2006 (UTC)