Active Site, Catalytic Cycle, and Iodination Reactions of Vanadium Iodoperoxidase: A Computational Study

A combined computational study using molecular surfaces and Poisson-Boltzmann electrostatic potentials for proteins and quantum calculations on complexes representing the vanadate cofactor throughout the catalytic cycle is employed to study the activity of vanadium iodoperoxidase (VIPO) from alga Laminaria digitata. A model structure of VIPO is compared with available crystal structures of chloroperoxidases (VCIPOs) and bromoperoxidases (VBrPOs) focusing on properties of the active site that concern halogen specificity. It is found that VIPO displays distinctive features regarding electrostatic potentials at the site cavity and the local topography of the cavity entrance. Quantum calculations on cofactor stages throughout the catalytic cycle reveal that, while steps involving binding of hydrogen peroxide and halide oxidization agree with available data on VBrPO, final formation and subsequent release of hypohalous acid could follow a different pathway consisting of His476-assisted protonation of bonded hypoiodite and further displacement by a water molecule. Ab initio free energies of reaction computed to explore iodination of organic substrates predict strongly exoergonic reactions with HOI, whereas other possible iodination reagents give thermodynamically disfavored reactions.