Serine ionizing groups

An additional point should be noted from table 3.3. Whereas the amino acid side chains (R groups) that are normally charged at physiological pH are restricted to five amino acids (aspartic acid, glutamic acid, lysine, arginine, and sometimes histidine), a number of potentially ionizable R groups are part of other amino acids. These include cysteine, serine, threonine, and tyrosine. The ionization reac-... 

One problem associated with the yeast 2-hybrid system is that protein interactions that are dependent on posttranslational modifications that can occur only in mammalian cells, would not be detected. For example, monoubiquitinylation and serine phosphorylation of a Fanconi anemia complementation group D2 protein (FANC-D2) are both required for mediating cellular resistance to ionizing radiation (122), an interaction that would be missed using this approach. 

N8-hydroxyamino group is acylated with a carbon piece related to mevalonic acid — acetic acid, fnwts- 3-methylglutacomc acid, cis or trans 5-hydroxy-3-methylpent-2-enoic acid (63). In albomycin S2, the hydroxyl group of the first serine is linked to a pyrimidine moiety by means of sulfur (137), the substantial literature in the U.S.S.R. on this antibiotic has been reviewed through 1964 (81). Ferric ion combines with the trihy-droxamate center concomitant with the ionization of three hydrogen ions. 

Finally, a molecule of water participates in the chemistry of catalysis. The HO" group attacks the covalently bound part of the substrate (dietary protein), resulting in its discharge fmm the chymotrypsin molecule (Figure 2.WF). The H of water then binds to Ser 195, regenerating the serine group to its iriitial non-ionized state. 

The AChE active site has two well defined subsites. The esteratic subsite contains a serine residue to which the acetyl group of the transmitter, the phosphorous of the OPs, and the carbamoyl carbon of the carbamates all bind. The anionic subsite contains an ionized carboxylic acid that binds the charged trimethylammonium group of the neurotransmitter. There is no clearly indicated interaction between this subsite and any part of the inhibitor molecules. Their leaving groups may bind to a different region in the active site from the substrate (48), or a charge-transfer complex may be involved in the... 

We have evidence that both the OH group of one serine residue and the imidazole group of one histidine residue are involved in the catalytic reaction. We have evidence that the serine OH is acylated by the substrate during the reaction sequence, while the imidazole group remains free and ionizable. 

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