CISD1 Protein, Human (His)

The CISD1 protein functions as an L-cysteine transaminase, facilitating the reversible transfer of the amino group from L-cysteine to the alpha-keto acid 2-oxoglutarate. This enzymatic process results in the formation of 2-oxo-3-sulfanylpropanoate and L-glutamate. The catalytic cycle is orchestrated in the presence of the pyridoxal 5'-phosphate (PLP) cofactor, which initiates transamination by forming an internal aldimine with the epsilon-amino group of the active site Lys-55 residue on the enzyme (PLP-enzyme aldimine). This internal aldimine is subsequently displaced by the formation of an external aldimine with the substrate amino group (PLP-L-cysteine aldimine). The external aldimine undergoes deprotonation, leading to the formation of a carbanion intermediate. In the presence of 2-oxoglutarate, this intermediate regenerates PLP, ultimately yielding the final products 2-oxo-3-sulfanylpropanoate and L-glutamate. The active site lysine residue is implicated in controlling proton transfer in the carbanion intermediate, while PLP stabilizes the carbanion structure through electron delocalization, a phenomenon known as the electron sink effect. Additionally, CISD1 plays a crucial role in regulating the maximal capacity for electron transport and oxidative phosphorylation and may be involved in iron-sulfur cluster shuttling and/or redox reactions. Notably, it can transfer the [2Fe-2S] cluster to an apo-acceptor protein, particularly under oxidative stress conditions, suggesting a role as a redox sensor that regulates mitochondrial iron-sulfur cluster assembly and iron trafficking.