Disease relevance of Gclc

• D. melanogaster GCLC (DmGCLC) and the candidate DmGCLM were expressed separately in Escherichia coli, purified, mixed, and then subjected to gel filtration, where they eluted as an approximately 140-kDa complex [1].

High impact information on Gclc

• The hypothesis that overexpression of glutamate-cysteine ligase (GCL), which catalyzes the rate-limiting reaction in de novo glutathione biosynthesis, could extend life span was tested in the fruit fly, Drosophila melanogaster [2].
• The GCL protein content of the central nervous system was elevated dramatically in the presence of either global or neuronal drivers [2].
• Mutation of the 3 cysteine residues allowed DmGCLM to associate with DmGCLC, but inhibited the formation of intersubunit disulfides [3].
• Glutamate-cysteine ligase (GCL) has a key influence on glutathione homeostasis [3].
• This caused a 2-fold reduction in the catalytic efficiency of Drosophila GCL, although activity remained significantly higher than the catalytic subunit alone [3].

Biological context of Gclc

• The modifier subunit of Drosophila glutamate-cysteine ligase regulates catalytic activity by covalent and noncovalent interactions and influences glutathione homeostasis in vivo [3].

Associations of Gclc with chemical compounds

• Enzyme kinetic analyses showed that DmGCLC has a K(m) for glutamate of 2.88 mm, but when complexed with DmGCLM, the K(m) for glutamate is 0.45 mm [1].
• A further mechanism for control of D. melanogaster GCL was found to be induction of DmGCLC by tert-butylhydroquinone in S2 cells [1].

Physical interactions of Gclc

• DmGCLC co-immunoprecipitated with DmGCLM from S2 cell extracts, suggesting that they also associate in vivo [1].

References