Hi Roberto:

You could try an expensive way, using Glycosilation inhibitors.
Tunicamycine for example Inhibits N-Glycosilation. I know there are also
commercial inhibitors for O-Glycosilation but I can't remember any right
now. You add them to the cultures when you produce your protein so that
all the proteins produced will not have glycosilation. The only problem is
that you need to standardize the optimum concentration that makes all your
protein be totally sugar free. However, glycosilation inhibitors tend to
be quite toxic, and you can end up killing your bug before you get your
protein sugar free and if you need lots to produce enough protein it could
be expensive.

I tried it a few years ago with Aspergillus fumigatus and A. nidulas
proteins and it worked very well. I wasn't crystallising them then, so I
don't know if it would have made anything better, but it did work for what
I needed.

When you say that endo-H doesn't do the job is it that the protein doesn't
loose any sugars or is it that it doesn't run (in gel) according to the
theoretical fully sugar free size? What I mean is that its not rare for
proteins from things like fungus and other "messy" organisms to have an
anomalous behavior in gel. If you follow the de-glycosilation process
slowly, you may realize that you have actually eliminated all the
glycosilations and that your sugar free protein may be running a bit
higher that it should.
In the .gif I’ve attached in the mail you can see an experiment in which
after deglycosilation with Endo-H all glycosilation sites had been
eliminated but the protein was still running about 10 kDa bigger that
according to sequence. So it could be that you protein is fine.

Hope some of this long mail is usefull.

Juan

Juan Sanchez-Weatherby
PhD Student
School of Bilogical Sciences
University of East Anglia



-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of
Roberto Steiner
Sent: 02 February 2006 13:18
To: Paul McEwan
Cc: [EMAIL PROTECTED]
Subject: Re: [ccp4bb]: off-topic: deglycosylation

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Dear Paul,

sometimes NOT removing all sugars might even be a good thing.
See for example, the case of quercetin 2,3 dioxygenase (quercetinase) from
A.japonicus where sugar chains are involved in the formation of a homodimer.
We never managed to remove all sugars and the protein crystallized very well.
(Crystals diffracted too, btw)

Roberto



Quoting Paul McEwan <[EMAIL PROTECTED]>:

> ***  For details on how to be removed from this list visit the  ***
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>
>
> I'm currently working with a glycoprotein and am having great difficulty
> deglycosylating it for crystallisation. I can completely remove the sugars
> very easily when the protein is denatured (not much good when you're
wanting
> to crystalise it), but seems completely resistant to treatment with endo
H or
> pngase F when done under native conditions. Any hints on getting this to
work
> would be greatly appreciated.
>
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> Dr Paul A. McEwan
> Protein Crystallography Group
> Centre for Biomolecular Science
> Clifton Boulevard
> University of Nottingham
> Nottingham
> NG7 2RD
> Tel: 0115 8468009
> http://www.nottingham.ac.uk/~pazxtal
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-- 
Dr. Roberto Steiner
Randall Division of Cell and Molecular Biophysics
New Hunt's House
King's College London
Guy's Campus
London, SE1 1UL
Phone +44 (0)20-7848-8216
Fax   +44 (0)20-7848-6435
e-mail [EMAIL PROTECTED]





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