This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cysteine dioxygenase (CDO, EC 1.13.11.20) is an Fe2+ metalloenzyme that adds molecular oxygen to the thiol group of cysteine to form the sulfinic acid called cysteinesulfinate. By catalyzing the first step in the oxidative metabolism of cysteine, CDO plays a key role in cysteine catabolism, in provision of cysteine carbon for gluconeogenesis or oxidative metabolism, in taurine synthesis, and in supply of inorganic sulfur for sulfation reactions. Perhaps more importantly, CDO is responsible for ensuring the maintenance of low cellular cysteine concentrations and preventing its cytotoxic and excitotoxic effects. Human clinical data strongly suggests the existence of genetic polymorphisms in CDO, with low expression of functional CDO being associated with the occurrence, severity, or rate of progression of rheumatoid arthritis as well as several chronic neurological disorders (e.g., motor neuron disease, Alzheimers disease).Very little is known about the structure or catalytic mechanism of CDO other than its amino acid sequence, substrate specificity, and its single iron atom that is required for catalytic activity. Searches (BLASTP) of existing databases for proteins with similar domain structures yield a number of CDOs or putative gene products that are homologous to CDO but no other homologous proteins.
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