Catalytic oxidation of zinc/sulfur coordination sites in proteins by selenium compounds.
Zinc/thiolate (cysteine) coordination occurs in a very large number of proteins. These coordination sites are thermodynamically quite stable. Yet the redox chemistry of thiolate ligands confers extraordinary reactivities on these sites. The significance of such ligand-centered reactions is that they affect the binding and release of zinc, thus helping to distribute zinc, and perhaps controlling zinc-dependent cellular events. One new aspect focuses on the thiolate ligands of zinc as targets for the redox action of selenium compounds. A distinctive feature of this chemistry is the capacity of selenols to catalyze the oxidation of zinc/thiolate sites. We here use a chromophoric compound, 2-nitrophenylselenocyanate, to investigate its reaction mechanism with the zinc/thiolate clusters of metallothionein, a protein that is a cellular reservoir for zinc and together with its apoprotein, thionein, is involved in zinc distribution as a zinc donor/acceptor pair. The reaction is particularly revealing as it occurs in two steps. A selenenylsulfide intermediate is formed in the fast oxidative step, followed by the generation of 2-nitrophenylselenol that initiates the second, catalytic step. The findings demonstrate the high reactivity of selenium compounds with zinc/thiolate coordination sites and the potent catalytic roles that selenoproteins and selenium redox drugs may have in affecting gene expression via modulation of the zinc content of zinc finger proteins.
Chen
Y
Y
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Maret
W
W
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002384:Catalysis; D003124:Colorimetry; D003545:Cysteine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D008668:Metallothionein / Q000737:chemistry / Q000187:drug effects*; D008956:Models, Chemical; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011485:Protein Binding; D012643:Selenium / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013455:Sulfur / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D016588:Anticarcinogenic Agents; D008024:Ligands; D009570:Nitriles; C044301:2-nitrophenyl selenocyanic acid; D013455:Sulfur; D008668:Metallothionein; D012643:Selenium; D015032:Zinc; D003545:Cysteine