Role of CO2 in proton activation by histidine decarboxylase (pyruvoyl)

The amino acid decarboxylases that use an intrinsic pyruvoyl cofactor have been viewed in terms of the pyridoxal-P paradigm whereby a Schiff base is formed between the enzyme-bound cofactor and the substrate, setting up a cation sink for electrons of the C alpha-CO2- bond, ejecting CO2, and the reversal of these steps with a proton with overall retention stereochemistry. With histidine decarboxylase (pyruvoyl) it is found that the presence of CO2 is required for T-exchange between histamine and water. Since the forward reaction including formation of the C-H bond does not require added CO2, it might be assumed that the CO2 that is formed in the fragmentation step is retained by the enzyme perhaps to assist in proton transfer. No such requirement for CO2 has been reported for the pyridoxal-P-dependent decarboxylases which are generally thought to liberate CO2 prior to proton transfer. In seeking a connection between bound CO2 and proton transfer in the histidine decarboxylase reaction, one is reminded of the carboxybiotin enzymes also known for an invariant stereochemistry of retention and for the requirement that the biotin be in the carboxylated form for H-exchange to occur. Perhaps the bound CO2 of histidine decarboxylase forms a carbamate by addition to Lys155 or to an amide group of the active site. The new carboxy group could then be the vehicle for protonating the carbon from which it originated, giving overall retention of the stereochemistry at the alpha-C.(ABSTRACT TRUNCATED AT 250 WORDS)