I did remember the protein modification technique, which is reductive
methylation.

-- 
Kendall W. Nettles, PhD
Assistant Professor
Department of Biochemistry
The Scripps Research Institute
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Jupiter Fl 33458

office 561-799-8851
fax 561-799-8805
cell 561-306-7566




From: Schneider Sabine <[EMAIL PROTECTED]>
Reply-To: Schneider Sabine <[EMAIL PROTECTED]>
Date: Thu, 22 Feb 2007 14:08:44 -0000
To: <[email protected]>
Conversation: Crystallisation of a extremly soluble protein
Subject: [ccp4bb] Crystallisation of a extremly soluble protein

Hi everyone,
 
I am trying to crystallise an extremely soluble and charged protein. It is
~30kDa and has an estimated PI of 5.2 and theoretical charge over pH range
4-10 from + 24 to -29. It is still happy at a concentration of 190mg/ml and
fully reconstituted with its ligand.
 
I have tried high throughput crystallisation with 10 different screens from
Nextal with concentrations of  60, 100 and 150mg/ml with no NaCl and NaCl
concentrations of 100mM, 300mM and 1M in either Hepes pH 8 or Tris-HCl pH
7.5. 
 
The distribution of heavy precipitation, light crystalline precipitation and
clear drops through out the screens locks like I am in the right
concentration range around the 100mg/ml, but I am not getting any real hit.
There are some drops with extreme phase separation. I also tried changing
the temperature from 20C to 4C.
 
I chased up a few conditions with this strong phase separation (or where I
imagined little objects...) by manual screening and also adding additives
like 3% Succrose, 50-200mM LiCl, 100mM EDTA, varying the PEGs (1500, 3350,
4000, 6000, 8000) as well as adding NaCl  to the reservoir solution in
sitting as well as hanging drop screens. But I am just getting nowhere -
either just precipitation or the drop stays clear with the strong phase
separation.
 
I also re-cloned it with chopping of a few more residues on the N-term where
according to a secondary structure prediction a helix starts and it is still
very happy at high concentrations, but again nothing in the high-throughput
screens. 
 
Has anyone any suggestions what else I could try?
 
Thanks!
 
Sabine
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