ION-PAIR FORMATION OF PHOSPHORYLATED AMINO-ACIDS AND LYSINE AND ARGININE SIDE-CHAINS - A THEORETICAL-STUDY

Protein phosphorylation is one of the major signal transduction mechan isms for controlling and regulating intracellular processes, Phosphory lation of specific hydroxylated amino acid side chains (Ser, Thr, Tyr) by protein kinases can activate numerous enzymes; this effect can be reversed by the action of protein phosphatases. Here we report ab init io (HF/6-31G and Becke3LYP/6-31G*) and semiempirical (PM3) molecular orbital calculations pertinent to the ion pair formation of the phosph orylated amino acids with the basic side chains of Lys and Arg, Methyl -, ethyl-, and phenylphosphate, as well as methylamine and methylguani dinium were used as model compounds for the phosphorylated and basic a mino acids, respectively. Phosphorylated amino acids were calculated a s mono- and divalent anions, Our results indicate that the PSer/PThr i on pair interaction energies are stronger than those with PTyr, Moreov er, the interaction energies with the amino group of Lys are generally more favorable than with the guanidinium group of Arg, The Lys amino groups form stable bifurcated hydrogen bonded structures; while the Ar g guanidinium group can form a bidentate hydrogen bonded structure, Re asonable values for the interaction free energies in aqueous solution were obtained for some complexes by the inclusion of a solvent reactio n field in the computation (PM3-SM3). (C) 1996 Wiley-Liss, Inc.