Sandbox Reserved 771: Difference between revisions
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[[Image:Dimerized_color.jpg|right| | [[Image:Dimerized_color.jpg|right|300px]] | ||
'''Glutathione synthetase''' (GSS) is an homo-dimeric, ATP-depending ligase responsible for the condensation of γ-Glutamylcysteine and glycine to form Glutathione (GSH) during the second step of the glutathione biosynthesis pathway <ref>PMID:19672693</ref>. '''Glutathione''' is considered to be one of the most abundant and important antioxidants present across many bacterial (cyano- and proteobacteria), and all plant & mammalian cells <ref>http://www.ncbi.nlm.nih.gov/protein/NP_000169.1</ref>. In addition to protecting cells from the oxidative damage caused by free radicals, it is believed to be involved in the detoxification of xenobiotics, toxins in the blood, and even amino acid transport <ref>PMID:21683691</ref>. | '''Glutathione synthetase''' (GSS) is an homo-dimeric, ATP-depending ligase responsible for the condensation of γ-Glutamylcysteine and glycine to form Glutathione (GSH) during the second step of the glutathione biosynthesis pathway <ref>PMID:19672693</ref>. '''Glutathione''' is considered to be one of the most abundant and important antioxidants present across many bacterial (cyano- and proteobacteria), and all plant & mammalian cells <ref>http://www.ncbi.nlm.nih.gov/protein/NP_000169.1</ref>. In addition to protecting cells from the oxidative damage caused by free radicals, it is believed to be involved in the detoxification of xenobiotics, toxins in the blood, and even amino acid transport <ref>PMID:21683691</ref>. | ||
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As stated previously, the catalytic active site of GSS is composed of the G-loop, S-loop, and A-loop. The G-loop has been termed the “<scene name='56/564047/Glycine_triad/1'>Glycine Triad</scene>” due to the contribution of three glycine residues in this loop to the enzymatic activity of GSS – '''Gly369''', '''Gly370''', and '''Gly371'''. While all three residues are essential to the activity of the enzyme, kinetic experiments have shown Gly369 and Gly370 to have much more critical roles than Gly371. G369V and G370V variants were found to contain a mere 0.7% and 0.3% of the activity of the wild type GSS enzyme, respectively. G371V mutants still contained approximately 13% of the wild type activity, indicating a level of importance similar to the Asp458 residue of the A-loop. These experimental results suggest that the mechanism of activity interference lies in a decreased ligand binding and failure to close the active site once the ligand has bound. | As stated previously, the catalytic active site of GSS is composed of the G-loop, S-loop, and A-loop. The G-loop has been termed the “<scene name='56/564047/Glycine_triad/1'>Glycine Triad</scene>” due to the contribution of three glycine residues in this loop to the enzymatic activity of GSS – '''Gly369''', '''Gly370''', and '''Gly371'''. While all three residues are essential to the activity of the enzyme, kinetic experiments have shown Gly369 and Gly370 to have much more critical roles than Gly371. G369V and G370V variants were found to contain a mere 0.7% and 0.3% of the activity of the wild type GSS enzyme, respectively. G371V mutants still contained approximately 13% of the wild type activity, indicating a level of importance similar to the Asp458 residue of the A-loop. These experimental results suggest that the mechanism of activity interference lies in a decreased ligand binding and failure to close the active site once the ligand has bound. | ||
</StructureSection> | |||
==Alternative Splicing Variants <ref>PMID:19672693</ref>== | ==Alternative Splicing Variants <ref>PMID:19672693</ref>== | ||
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Studies suggest that the rarity of this disorder can be attributed to the fact it is autosomal recessive and thus both copies of the cell's chromosome must contain the genetic coding for the disorder. Each of the parents must carry a single copy of the mutated <i>gss</i> gene, thus displaying no physical symptoms, and both must pass their mutated copy on to the child. | Studies suggest that the rarity of this disorder can be attributed to the fact it is autosomal recessive and thus both copies of the cell's chromosome must contain the genetic coding for the disorder. Each of the parents must carry a single copy of the mutated <i>gss</i> gene, thus displaying no physical symptoms, and both must pass their mutated copy on to the child. | ||