Tandem Mass Spectrometric Evidence for the Involvement of a Lysine Basic Side Chain in the Coordination of Zn(II) Ion within a Zinc-bound Lysine Ternary Complex

We present the tandem mass spectrometry applications carried out to elucidate the coordination structure of Zn(II) bound lysine ternary complexes, (Zn+Lys+Lys-H)⁺ , which is a good model system to represent a simple (metallo)enzyme-substrate complex (ES). In particular, experimental efforts were focused on revealing the involvement of a lysine side chain ε -amino group in the coordination of Zn²⁺ divalent ions. MS/MS fragmentation pattern showed that all the oxygen species within a complex fell off in the form of H₂O in contrast to those of other ternary complexes containing amino acids with simple side chains (4-coordinate geometries, Figure 1a), suggesting that the lysine complexes have different coordination structures from the others. The participation of a lysine basic side chain in the coordination of Zn(II) was experimentally evidenced in MS/MS for Nε -Acetyl-L-Lys Zn(II) complexes with acetyl protection groups as well as in MS/MS for the ternary complexes with one NH₃ loss, (Zn+Lys+Lys-NH₃-H)⁺ . Detailed structures were predicted using ab initio calculations on (Zn+Lys+Lys-H)⁺ isomers with 4-, 5-, and 6-coordinate structures. A zwitterionic 4-coordinate complex (Figure 7d) and a 5-coordinate structure with distorted bipyramidal geometry (Figure 7b) are found to be most plausible in terms of energy stability and compatibility with the experimental observations, respectively.