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At the risk of going over previously covered ground...

You *should* be able to get Mass-Spec data from a crystal. Our Mass-Spec
guys here routinely cut bands out of stained SDS-PAGE gels and get accurate
enough peptide masses to ID unknown proteins... Loss of 28 residues should
easily be detectable.


On 1/12/05 9:43 pm, "[EMAIL PROTECTED]"
<[EMAIL PROTECTED]> thought:

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> 
> 
> Apologies for continuing to top-post here...
> 
> If the cleavage would only remove 28 amino acids from a 500 amino acid
> chain, it could easily be missed by SDS-PAGE, although mass spec would
> catch it.  However, I don't think you can get enough sample from a
> dissolved crystal to run mass spec.
> 
> To the original poster: you need to describe the electron density break to
> us in more detail, or better yet, direct us to some screenshots.  What is
> your resolution?  How good is the electron density in the vicinity of the
> break?  Can you see the side chains of residues 28 and 29?  A true peptide
> bond cleavage will leave free amino and carboxy termini which will not fit
> in the same space as a peptide bond - even at modest resolution, you should
> be able to see that C-alpha #28 and C-alpha #29 are not the canonical 3.8 A
> apart; at high resolution, you would hopefully see the extra oxygen of the
> COOH terminus.
> 
> - Matt
> 
> --
> Matthew Franklin                     phone:(917)606-4116
> Senior Scientist, ImClone Systems      fax:(212)645-2054
> 180 Varick Street, 6th floor
> New York, NY 10014
> 
> [EMAIL PROTECTED] wrote on 12/01/2005 11:59:14 AM:
> 
>> ***  For details on how to be removed from this list visit the  ***
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>> 
>> 
>> Short answer - CAN'T BE.
>> 
>> If you dissolve crystals and run SDS PAGE and/or mass-spec and do not see
> the
>> cleavage it means that there is an error in your electron density. Some
>> disorder is really hard to model even having the atomic resolution data,
> and
>> some main chain bonds might have much lower density than the others
> creating
>> an appearance of cleavage.
>> 
>> Petr
>> 
>> On Thursday 01 December 2005 02:01 am, Jinkwang wrote:
>>> Hi all,
>>> Routine MR solution of a mutant structure was an easy task until I
> found a
>>> clear cleavage within the polypeptide chain. This cleavage is
> reproducible
>>> only in crystal structure, and biochemical studies such as SDS-PAGE,
>>> N-terminal sequencing or Mass spectra never indicate any cleavage in
> the
>>> chain.
>>> 
>>> 
>>> 
>>> The protein has about 700 amino acids, divided into alpha (200 a.a) and
>>> beta (500) chains. The cleavage is found at 28-29 of the beta chain in
> the
>>> crystal. Wondering whether this could occur only in crystal states, the
>>> crystals were dissolved, but the biochemical studies did not show any
>>> cleavage, but crystal structure once again shows.
>>> 
>>> 
>>> 
>>> Any comments are highly appreciated.
>>> 
>>> 
>>> 
>>> Regards,
>>> 
>>> Jin Kwang
> 
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