CYSTEINE DIOXYGENASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 半胱氨酸双加氧酶(CDO，EC 1.13.11.20)是一种Fe2+金属酶，它将分子氧加到半胱氨酸的硫醇基团上，形成亚磺酸，称为半胱氨酸亚磺酸。通过催化半胱氨酸氧化代谢的第一步，CDO在半胱氨酸的分解代谢、糖异生或氧化代谢的半胱氨酸碳的提供、牛磺酸的合成和硫化反应的无机硫的供应中起着关键作用。也许更重要的是，CDO负责确保维持较低的细胞半胱氨酸浓度，并防止其细胞毒性和兴奋毒性效应。人类临床数据强烈提示CDO存在基因多态性，功能性CDO的低表达与类风湿关节炎和几种慢性神经疾病(如运动神经元病、阿尔茨海默病和S病)的发生、严重程度或进展速度有关。 除了它的氨基酸序列、底物特异性以及催化活性所需的单个铁原子外，人们对CDO的结构或催化机理知之甚少。对现有数据库中具有相似结构域结构的蛋白质的搜索(BLASTP)会产生一些与CDO同源但不与其他同源蛋白质同源的CDO或假定的基因产物。

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, Alzheimer¿¿¿¿¿"s 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.