Why vanadate and not molybdate as a cofactor for haloperoxidases?

Question of the Week, 28.6.2011

Vanadium haloperoxidases are enzymes found in several seaweeds and fungi, which catalyze the two-electron oxidation of halide ions by hydrogen peroxide, resulting in a hypohalous acid which in turn can further halogenate several organic compounds.

Vanadium (V) ion is present in the active site of this enzymes presenting a trigonal bipyramidal geometry, bound to a hystidine aminoacid of the active center and forming hydrogen bonds with several surrounding aminoacids. During the catalytic reaction, one of the intermediates is a peroxo species formed with the vanadium (V). Molybdenum is a well-known catalyst and can form very reactive oxodiperoxo species, being much more reactive in solution than vanadium. Since molybdenum and vanadium have similar ionic radii, H. Vilter suggested the use of molybdate (VI) as the active center of the vanadium haloperoxidases, but surprisingly the substitution of vanadate by molybdate resulted in an almost total loss of activity from the enzyme.

Some studies, especially by computational methods, indicate that this loss of activity might be related with the different catalytic mechanism of both ionic species, as well as the possible coordination that the different ions can go through with the amino acids in the active site of the enzyme. But is interesting to note that the presence of molybdenum in the natural environment of the species that carry these enzymes (like seaweeds for example) is quite higher than for vanadium, thus leading to the question why in nature the enzymes evolved and adapted to have vanadium in the active center and not molybdenum, when a properly adapted haloperoxidase with a molybdate active center would probably be much more reactive.