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Nickel‐substituted iron‐dependent cysteine dioxygenase: Implications for the dioxygenation activity of nickel model compounds
Author(s) -
Attia Amr A. A.,
SilaghiDumitrescu Radu
Publication year - 2018
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.25564
Subject(s) - chemistry , cysteine , redox , moiety , sulfur , nickel , ligand (biochemistry) , catalysis , adduct , stereochemistry , catalytic cycle , photochemistry , medicinal chemistry , inorganic chemistry , organic chemistry , enzyme , biochemistry , receptor
Reported here is a density functional theory study on the ability of Ni‐substituted iron‐dependent cysteine dioxygenase (CDO) to catalyze the oxidation of cysteine to cysteine sulfinic acid. The first steps of the commonly accepted mechanism for CDO, the O 2 activation mechanism, suggests the binding of O 2 to the metal ion (where redox isomerism takes place converting O 2 toO 2 − ) followed by the attack of the distal oxygen atom on the cysteine sulfur—in line with most previous evidence. An alternative mechanism entailing the attack of the cysteine sulfur on the proximal oxygen atom of the dioxygen moiety to form a persulfenate intermediate without any redox exchange between the metal ion and the O 2 ligand, is supported by an X‐ray crystal structure showing a CDO with a bound cysteine persulfenate, and also supported by data on the oxidation of thiols catalyzed by Ni(II) compounds. Our results show that the O 2 activation mechanism with a Ni‐substituted active site follows the same pattern as native CDOs albeit with much higher energy barriers for the formation of the intermediates suggesting that the reaction might not be biologically feasible. Conversely, the immediate cleavage of the persulfenate SO bond in the alternative mechanism suggests that cysteine persulfenate might not be a true intermediate in catalytic cycle of CDOs.