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Several methods are available:
 
Several methods are available:
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1. Modification of lysine residues
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2.1. Modification of lysine residues
    
This method, pioneered by the Rayment laboratory, involves the methylation -- under reducing conditions -- of lysine residues. This increases the hydrophobicity of the modified lysine sidechains, reduces the overall solubility of the protein, and -- for some proteins -- promotes the formation of ordered crystal contacts.  
 
This method, pioneered by the Rayment laboratory, involves the methylation -- under reducing conditions -- of lysine residues. This increases the hydrophobicity of the modified lysine sidechains, reduces the overall solubility of the protein, and -- for some proteins -- promotes the formation of ordered crystal contacts.  
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2. Modification of cyteine residues  
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2.2. Modification of cyteine residues  
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This method involves the carboxymethylation -- under reducing conditions -- of single cysteine residues. This effectively neutralizes the cysteine residues (some of which are chemically reactive), increase the overall solubility of proteins and can help prevent aggregation and denaturation problems of proteins.
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This method involves the carboxymethylation -- under reducing conditions -- of single cysteine residues. This effectively neutralizes the cysteine residues (some of which are chemically reactive), increases the overall solubility of the protein and can help prevent aggregation and denaturation problems.
    
References:
 
References:
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Eiler S et al. (2001) Protein Expr Purif. 22(2):165-73
 
Eiler S et al. (2001) Protein Expr Purif. 22(2):165-73
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http://www.ionsource.com/Card/cmc/method.htm  -- A protocol for carbocymethylation
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http://www.ionsource.com/Card/cmc/method.htm  -- A protocol for carboxymethylation
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