Home Blog of Signal Transduction Apoptosis Apoptosis related Excess copper catalyzes protein disulfide bond formation in the bacterial periplasm but not in the cytoplasm

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Excess copper catalyzes protein disulfide bond formation in the bacterial periplasm but not in the cytoplasm

Copper avidly binds thiols and is redox-active, and it follows that one element of copper toxicity may be the generation of undesirable disulfide bonds in proteins. In the present study copper oxidized the model thiol N-acetylcysteine in vitro. Alkaline phosphatase (AP) requires disulfide bonds for activity, and copper activated reduced AP both in vitro and when it was expressed in the periplasm of mutants lacking their native disulfide-generating system. However, AP was not activated when it was expressed in the cytoplasm of copper-overloaded cells. Similarly, this copper stress failed to activate OxyR, a transcription factor that responds to the creation of a disulfide bond. The elimination of cellular disulfide-reducing systems did not change these results. Nevertheless, in these cells the cytoplasmic copper concentration was high enough to impair growth and completely inactivate enzymes with solvent-exposed [4Fe-4S] clusters. Experiments with N-acetylcysteine determined that the efficiency of thiol oxidation is limited by the sluggish pace at which oxygen regenerates copper(II) through oxidation of the thiyl radical-Cu(I) complex. We conclude that this slow step makes copper too inefficient a catalyst to create disulfide stress in the thiol-rich cytoplasm, but it can still impact the few thiol-containing proteins in the periplasm. It also ensures that copper accumulates intracellularly in the Cu(I) valence.

 

Comments：
The study described above investigated the effects of copper toxicity on proteins. It was found that copper can bind to thiols, such as N-acetylcysteine, and generate disulfide bonds in proteins. This was shown to activate alkaline phosphatase (AP) in the periplasm of cells, but not when expressed in the cytoplasm. This is because the high concentration of copper in the cytoplasm makes it inefficient at generating disulfide bonds, but still impacts thiol-containing proteins in the periplasm. The slow rate of oxygen regeneration of copper(II) was found to limit the efficiency of thiol oxidation and contribute to the accumulation of intracellular copper in the Cu(I) valence. Overall, the results of this study suggest that copper toxicity can have a significant impact on proteins, both in terms of disulfide bond formation and enzyme activity.

Related Products

Cat.No. Product Name Information
S1623 Acetylcysteine (N-acetylcysteine) Acetylcysteine (N-acetyl-l-cysteine, NAC,N-acetylcysteine) is a ROS(reactive oxygen species) inhibitor that antagonizes the activity of proteasome inhibitors. It is also a tumor necrosis factor production inhibitor. Acetylcysteine(N-acetyl-l-cysteine) suppresses TNF-induced NF-κB activation through inhibition of IκB kinases. Acetylcysteine(N-acetyl-l-cysteine) induces apoptosis via the mitochondria-dependent pathway. Acetylcysteine(N-acetyl-l-cysteine) inhibits ferroptosis and virus replication.Solutions are unstable and should be fresh-prepared.

Related Targets

Apoptosis related TNF-alpha NF-κB Antiviral Ferroptosis ROS