Evidence for an N-Halohistidyl Intermediate in the Catalytic Cycle of Vanadium Chloroperoxidase (VCPO) and an Artificial Enzyme Derived from VCPO: A Computational Investigation.

Vanadium haloperoxidases play an important catalytic role in the natural production of antibiotics which are difficult to make in the laboratory. Understanding the catalytic mechanism of these enzymes will aid in the production of artificial enzymes useful in bioengineering the synthesis of drugs and useful chemicals. However, the catalytic mechanism remains not fully understood yet. In this paper, we investigate one of the key steps of the catalytic mechanism using QM/MM. Our investigation reveals a new N-halohistidyl intermediate in the catalytic cycle of vanadium chloroperoxidase (VCPO). This new intermediate, in turn, can explain the known inhibition of the enzyme by substrate under acidic conditions (pH < 4). Additionally, we examine the possibility of replacing V in VCPO by Nb or Ta using QM modeling. We report the new result that the Gibbs free energy barriers of several steps of the catalytic cycle are lower in the case of artificial enzymes, incorporating NbO 4 3 − or TaO 4 3 − instead of VO 4 3 − . Our results suggest that these new artificial enzymes may catalyze the oxidation of halide faster than the natural enzyme. The catalytic mechanism of vanadium chloroperoxidase is investigated using QM/MM, and evidence for a new N-halohistidyl intermediate is found in the last step of mechanism. When V is replaced with Nb or Ta, the barrier heights in the mechanism are calculated to be lower for some steps, using a QM model. Thus, we suggest that replacement of V with Nb or Ta may lead to an artificial enzyme with a faster rate of catalysis. [ABSTRACT FROM AUTHOR]