Proteins amino acid, critical positions

It should be noted that proteins have certain critical positions in their amino acid sequence. At such positions a change in the nature of the amino acid will almost always have an effect on its function, whereas at other non-critical positions amino acid substitutions seem to have little or no effect. A position may be critical either because its amino acid provides an essential reactive group on which the function of the protein depends, or because it is structurally important in that it helps to ensure the exact stereochemical position of a reactive group. It is usually found that positions within helical sections are non-critical. 

Chain length of sodium alkyl carboxylate Human skin irritancy Positive reactions to 22.5 mM solutions (%) Rat skin irritancy Assessed score for irritancy (macroscopic and microscopic). 0.25 M solutions for 15 min, once daily for 3 days Collagen disc swelling Change in thickness, critical micelle concentration (%) Extraction of stratum comeum Increase relative to water Proteins Amino acids (%) Ion conductance of stratum comeum Rate of change of conductance (Mohm/cm /min xlO" )... 

The critical feature of CREB protein activation is phosphorylation, which is required for CREB-mediated stimulation of transcription [16]. PKA phosphorylates CREB on a serine positioned at amino acid 133 in the CREB protein sequence. How phosphorylation activates... 

The second type of point mutation results in the replacement of one amino acid with another. Such mutations will have more or less of an effect depending on which amino acid is changed. Obviously, if a critical amino acid is replaced by one that is unable to provide the same function, the protein will lose some or all of its activity. Mutations within that Ras and Src genes are two examples in which point mutations lead to disease. In the case of the Ras protein, substitution of a single amino acid, most commonly at either position 12 or 61, is associated with the occurrence of several human tumors. In the case of the Src protein, a point mutation that occurs in a tyrosine residue leads to the constitutive activation of the protein and is associated once again with several types of tumors. 

A further consideration is the position of the sequon in relation to the primary structure of the protein. Statistical analysis of a large number of glycoproteins has indicated that the frequency of non-glycosylated sequons increases toward the C-terminus (Gavel and von Heijne, 1990). The critical distance appears to be 60 amino acid residues from the C-terminus when reduced glycan occupation occurs. This distance corresponds to the distance between the ribosome P-site and the active site of the OST and it has been hypothesized that the protein chain is not available for N-glycan attachment once it is released from the ribosome. However, this phenomenon of poor glycosylation efficiency toward the C-terminus does not appear to be universal for all proteins (Walmsley and Hooper, 2003). 

---