The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins

Uversky, Vladimir N

The side chain of glutamic acid contains two methylene group and the carboxylic acid functional group (see Fig. 2A ) that exists in a negatively charged deprotonated carboxylate with stroke, autism, amyotrophic lateral sclerosis, lathyrism, some forms of mental retardation and Alzheimer's disease. 58 The decreased glutamate release is associated with phenylketonuria leading to the developmental disruption of glutamate receptor expression. 59, 60 the excess glutamate in the extracellular space and promoting entrance of calcium to the cell via the NMDA receptor channels. This process is known as excitotoxicity, and it results in neuronal damage and eventual cell death. The excitotoxicity might occur as part of the ischemic cascade that is associated Figure 1 . amino acid determinants defining structural and functional differences between the ordered and intrinsically disordered proteins. (A) Fractional difference in the amino acid composition (compositional profile) between the typical IDPs from the DisProt database 49 and a set of completely ordered proteins 50 calculated for each amino acid residue. The fractional difference was evaluated as (C DisProt − C PDB )/C PDB , where C DisProt is the content of a given amino acid in a DisProt databse, and C PDB is the corresponding content in the data set of fully ordered proteins. Positive bars correspond to residues found more abundantly in IDPs, whereas negative bars show residues, in which IDPs are depleted. amino acid types were ranked according to their decreasing disorder-promoting potential. 47 (B) amino acid compositions of several data sets discussed in the text (DisProt, 49 UniProt, 51 PDB Select 25 50 and surface residues 48 ).