Conservative changes - glycosylated N

Ian A. York iayork at
Fri Jul 25 07:13:01 EST 2003

In article <Pine.LNX.4.44.0307242225140.20704-100000 at>,
Tom Anderson  <univ0938 at> wrote:
>I'm confused; to me, the reason seems obvious, which means i'm missing
>something! Getting rid of the asparagine will get rid of the glycosylation
>site, won't it? Since asparagine and glutamine are otherwise pretty
>similar, the change should have minimal other effect on the protein.

Asn to Gln will eliminate the glycosylation site, yes.  Asn and Gln are
similar, yes.  That's the problem.  I'm not changing Asn;  I'm changing
Asn that's covalently bound to a large carbohydrate.  Gln is *not*
particularly similar to Asn-CHO.

If you block N-glycosylation with, say, tunicamycin, there is massive
misfolding of proteins in the ER.  Essentially what you're doing there is
"mutating" Asn-CHO to Asn, and clearly that's *not* a particularly
conservative change, because it often destroys protein folding.  
Therefore, choosing something that's *similar* to Asn may be exactly what
I *don't* want to do, right?

Having said that, I don't know that there's a better solution, and will 
probably end up changing Asn to Gln anyway.  It's true that's what has 
worked for others, but after all for a lot of proteins you could probably 
get away with altering Asn to Pro anyway--lots of proteins are awfully 
forgiving.  I was hoping there was some kind of methodical test of this 
somewhere, not just someone else who shrugged and hoped.

    Ian York   (iayork at  <>
    "-but as he was a York, I am rather inclined to suppose him a
     very respectable Man." -Jane Austen, The History of England

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