C. Salinas et al., DOPACHROME TAUTOMERASE DECREASES THE BINDING OF INDOLIC MELANOGENESISINTERMEDIATES TO PROTEINS, Biochimica et biophysica acta. Protein structure and molecular enzymology, 1204(1), 1994, pp. 53-60
Dopachrome tautomerase (DCT) is a recently characterized enzyme contri
buting to the control of melanogenesis in mammals. The enzyme catalyze
s the rearrangement of L-Dopachrome (L-DC) to 5,6-dihydroxyindole 2-ca
rboxylic acid (DHICA), while the spontaneous rearrangement of L-DC lea
ds to 5,6-dihydroxyindole (DHI). Due to the lower reactivity of DHICA
in comparison to DHI, DCT could provide a protective mechanism against
the cytotoxicity of decarboxylated indolic melanogenic intermediates
by limiting the formation of these highly reactive decarboxylated spec
ies within melanocytes. We have followed the binding of radioactive me
lanogenic precursors to a model protein, bovine serum albumin (BSA). U
sing L-DC as initial melanin precursor, this binding was decreased by
DCT in a concentration-dependent manner. In the presence of tyrosinase
, the binding of L-Dopa-derived intermediates to BSA was also decrease
d by DCT and the percentage of decrease was even higher than using L-D
C as initial melanin precursor. SDS-PAGE followed by fluorographic det
ection of radioactive bands showed the formation of covalent adducts b
etween BSA and melanin precursors, as well as of aggregated forms of t
his protein. This aggregation was also diminished by DCT. These data i
ndicate that DCT could play a protective role against the cytotoxic ac
tion of decarboxylated indoles within mammalian melanocytes.