The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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

Glutamate-cysteine ligase (GCL) has a key influence on glutathione homeostasis. It has been proposed that mammalian GCL is regulated by the redox environment, and we show here that cysteine residues in the Drosophila melanogaster GCL modifier subunit (DmGCLM) can form covalent interactions with the catalytic subunit (DmGCLC) and modify its activity. Candidate components of intersubunit disulfides (Cys213, Cys214, and Cys267) were identified using matrix-assisted laser desorption ionization time-of-flight spectroscopy of iodoacetamide-modified DmGCLM as well as examination of the evolutionary conservation of cysteines. Mutation of the 3 cysteine residues allowed DmGCLM to associate with DmGCLC, but inhibited the formation of intersubunit disulfides. This caused a 2-fold reduction in the catalytic efficiency of Drosophila GCL, although activity remained significantly higher than the catalytic subunit alone. The cysteine mutant was also more sensitive to inhibition by glutathione than the unmodified holoenzyme. Notably, human GCLM could substitute for DmGCLM in modification of DmGCLC activity. The role of DmGCLM in vivo was examined by analysis of a Drosophila mutant (l(3)L0580) containing a P-element insertion in Gclm. We found that the P-element is not responsible for the lethal phenotype and separated the recessive lethal mutation from the P-element by recombination. This yielded two fully viable and fertile recombinants bearing the P-element insertion, which Western and Northern blotting indicated is a severely hypomorphic allele of Gclm. Glutathione levels were approximately 2-fold lower in the GclmL0580 mutants than in control strains, demonstrating the importance of DmGCLM in the regulation of glutathione homeostasis in vivo.[1]


WikiGenes - Universities