WEAK-INTERACTIONS IN METAL-COMPLEXES OF AMINO-ACIDS WITH A PHOSPHORYLATED SIDE-CHAIN - CONVERSION OF AROMATIC RING STACKING TO ELECTROSTATIC BONDING BY TYROSINE PHOSPHORYLATION

Ternary Cu(II) complexes with the phosphoesters of amino acids (A = O-phosphoserine (Pser) or 0-phosphotyrosine (Ptyr)) and basic amino acids (B - arginine (Arg) or lysine (Lys)), Cu(L-A)(L-B), have been studied by absorption and circular dichroism (CD) spectral, pH titration and X-ray diffraction methods. CD spectral magnitude anomaly in the d-d region at neutral pH was interpreted as due to the electrostatic interactions between the side chain phosphoester group of A and the protonated group of B. The stability constants for the ternary complexes were determined at 25-degrees-C and I = 0.1 and 1.0 M(KNO3), and the stability enhancement due to the ligand-ligand interactions was evaluated by calculating the equilibrium constant K for the following hypothetical equilibrium from the overall stability constant of each ternary species: Cu(L-A)(L-B') + Cu(L-A')(L-B) reversible (K) Cu(L-A)(L-B) + Cu(L-A')(L-B'), where A' refers to serine or tyrosine (Tyr) and B' to alanine and the interactions are possible only in Cu(L-A)(L-B). The ionic strength dependence of the log K values (> 0) indicated that Cu(L-A)(L-B) is stabilized by electrostatic interactions. X-ray crystal structure analysis of [Cu(bpy)(L-Tyr)ClO4] . 2H2O (bpy = 2,2'-bipyridine) revealed that the non-phosphorylated complex involves aromatic ring stacking between the Tyr phenol and coordinated bpy rings with the average spacing of 3.35 angstrom in a tetrahedrally distorted square-pyramidal structure with the two nitrogen atoms of bpy and the nitrogen and oxygen atoms of L-Tyr at the equatorial positions and an oxygen atom of the perchlorate ion at the axial position. The results show that the stacked Tyr phenol ring is phosphorylated to be involved in the electrostatic interactions with the positively charged side chain of Arg or Lys, which may be a possible mechanism of the conformational change due to Tyr phosphorylation in proteins.