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Hi,

You have to give a few things a go - see what is better. I typically try
subtilisin Carlsberg and thermolysin before anything else - these two
proteases are sufficiently nonselective. I typically try 5-6 different
exposure levels (either by time or by ratio) per protease, then SDS-PAGE
and MS the results.

Here's an example of what has worked (with a gel picture, too!)

http://www.xtals.org/pdfs/FliC_FliS.pdf

Artem
ex-PGP

Original Message:
-----------------
From: Pirkko Heikinheimo [EMAIL PROTECTED]
Date: Tue, 13 Jun 2006 10:51:42 +0300
To: [EMAIL PROTECTED], [EMAIL PROTECTED], [email protected]
Subject: Re: [ccp4bb]: boundaries of new constructs


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It would be nice if those who have had success on limited proteolysis 
could share which proteases they are using. We've tryed limited trypsin 
digestion but mostly end up with total hydrolysis or no visible effect 
(the target proteins have natural protease sensitive sites which we 
expect to be proteolysed and thus the effect be visible on a gel).

with best regards,
Pirkko Heikinheimo

Tim Gruene wrote:
> ***  For details on how to be removed from this list visit the  ***
> ***          CCP4 home page http://www.ccp4.ac.uk         ***
> 
> 
> I would recommend restricted proteolysis, i.e., a time series of digestion
> with various proteases. Start with concentration ratios of 1:500
> protease:your_protein and check the success by SDS-PAGE. The N-terminus
> can be determined by N-terminal sequencing. For the C-terminus you can try
> to scale up, run a gel filtration column or (probably better) an ion
> exchange column + GF and do a mass spec.
> 
> If mass spec does not work (proteins soluble at high salt concentrations
> only are a hinderence or if the domains are not well defined by the
> proteolysis), you can estimate the weight from SDS-PAGE and make use of
> the secondary structure prediction, available e.g. through the
> expasyserver (www.expasy.ch).
> 
> --
> Tim Gruene
> Institut fuer anorganische Chemie
> Tammannstr. 4
> D-37077 Goettingen
> 
> GPG Key ID = A46BEE1A
> 
> 
> On Mon, 12 Jun 2006, Wang, Yeming (NIH/NIEHS) [F] wrote:
> 
>> ***  For details on how to be removed from this list visit the  ***
>> ***          CCP4 home page http://www.ccp4.ac.uk         ***
>>
>>
>> Sorry for the off-topic question!
>>
>> My current construct of a new protein (has some homologs) doesn't seem
to be good and I have to make some new ones. I am just wondering how to
determine the N-terminus & C-terminus of new constructs if I am only
interested in structural study of a few domains. Any good methods or
softwares to recommend?  Thanks a lot!
>>
>> Yeming
>> ---------------------
>> Yeming Wang, Ph.D.
>> Laboratory of Structural Biology: Macromolecular Structure Group
>> National Institute of Environmental Health Sciences
>> National Institute of Health
>> Mailing Address:      Street Address:
>> NIEHS, MD F3-05       NIEHS, Building 101, Room F362
>> P.O. BOX 12233        111 T.W. Alexander Drive
>> RTP, NC 27709         RTP, NC 27709
>> Tel (o): 919-316-4634
>> E-mail: [EMAIL PROTECTED]
>>

-- 
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Pirkko Heikinheimo

Structural Biology and Biophysics,
Institute of Biotechnology,
P. O. Box 65,
FIN-00014 University of Helsinki, Finland

Visit address:
Biocenter 3, room 4320
Viikinkaari 3, 00790 Helsinki, Finland

http://www.biocenter.helsinki.fi/bi/xray/pirkko
e-mail: [EMAIL PROTECTED]
phone:  358-(0)9-191 58957
gsm:    358-(0)50-354 0713
fax:    358-(0)9-191 59940

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