Weak Antiferromagnetic Coupling via a Superexchange Interaction between Mn(II)–Mn(II) Ions: A QM/MM Study of the Active Site of Human Cytosolic X‑Propyl Aminopeptidase P

We investigate the dinuclear manganese, Mn(II)–Mn(II), active site of human cytosolic X-propyl aminopeptidase (XPNPEP1) by employing the QM/MM method. The optimized structure supports two manganese atoms at the active site and excludes the possibility of a single Mn(II) atom or another combination of divalent metal ions, Ca(II), Fe(II), an Mg(II). A broken-symmetry solution verifies an antiferromagnetically coupled state between the Mn(II)–Mn(II) pair, which is the ground state. From the energy difference between the high spin state (HS) and the broken-symmetry state (BS), we estimate the exchange coupling constant, J, to be 5.15 cm–1. Also, we observe multiple bridges (p orbitals) from the solvent and two carboxylates linking to the Mn(II)–Mn(II), which leads to the weakly antiferromagnetic interaction of d5–d5 electrons through superexchange coupling.