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Probes of the catalytic site of cysteine dioxygenase.

Authors: Chai, SC  Bruyere, JR  Maroney, MJ 
Citation: Chai SC, etal., J Biol Chem. 2006 Jun 9;281(23):15774-9. Epub 2006 Apr 11.
Pubmed: (View Article at PubMed) PMID:16611641
DOI: Full-text: DOI:10.1074/jbc.M601269200

The first major step of cysteine catabolism, the oxidation of cysteine to cysteine sulfinic acid, is catalyzed by cysteine dioxygenase (CDO). In the present work, we utilize recombinant rat liver CDO and cysteine derivatives to elucidate structural parameters involved in substrate recognition and x-ray absorption spectroscopy to probe the interaction of the active site iron center with cysteine. Kinetic studies using cysteine structural analogs show that most are inhibitors and that a terminal functional group bearing a negative charge (e.g. a carboxylate) is required for binding. The substrate-binding site has no stringent restrictions with respect to the size of the amino acid. Lack of the amino or carboxyl groups at the alpha-carbon does not prevent the molecules from interacting with the active site. In fact, cysteamine is shown to be a potent activator of the enzyme without being a substrate. CDO was also rendered inactive upon complexation with the metal-binding inhibitors azide and cyanide. Unlike many non-heme iron dioxygenases that employ alpha-keto acids as cofactors, CDO was shown to be the only dioxygenase known to be inhibited by alpha-ketoglutarate.

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CRRD Object Information
CRRD ID: 2301357
Created: 2008-10-08
Species: All species
Last Modified: 2008-10-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.