Mammalian Cysteine Dioxygenase

Abstract Cysteine dioxygenase (CDO) is a mononuclear nonheme Fe(II) enzyme that catalyzes the oxidation ofl‐cysteine tol‐cysteinesulfinic acid (CSA) by addition of both atoms of molecular oxygen to the cysteine sulfur. Mammalian CDO is highly expressed in the liver, the pancreas, the adipose tissue, the kidney and the lungs, and the CSA produced is further converted to either taurine or sulfate plus pyruvate. To maintain cysteine levels within the narrow range required for health, mammalian CDO is regulated by the modulation of enzyme turnover and through formation of a Cys93‐Tyr157 crosslink that increases its activity over 10‐fold. Imbalances in cysteine metabolism have been observed in several neurological disorders, and CDO has been identified as a tumor suppressor. Bacterial CDOs also exist, as do a variety of related thiol dioxygenases that have been less well studied. High‐resolution crystal structures of CDO reveal iron coordination by three histidines. Cysteine coordinates the iron by its amino and thiolate groups, leaving a sixth coordination site open for dioxygen. A cysteine persulfenate has been trapped in the active site, but despite substantial spectroscopic studies and theoretical calculations, the details of the mechanism are still a matter of debate and it is uncertain if this is an intermediate.