Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane crystals of the mitochondrial outer membrane channel VDAC (porin) from Neurospora crassa were incubated with a 20-amino-acid synthetic peptide corresponding to the N-terminal targeting region of subunit IV of cytochrome oxidase. The peptide caused disordering and contraction of the crystal lattice of the membrane arrays. Also, new stain-excluding features were observed on the peptide-treated arrays which most likely correspond to sites at which the peptide accumulates. The stain exclusion zones associated with binding of the targeting peptide (and with binding of apocytochrome c in an earlier study) have been localized on a two-dimensional density map of frozen-hydrated, crystalline VDAC previously obtained by cryo-electron microscopy. The results indicate that both the peptide and cytochrome c bind to protein "arms" which extend laterally between the channel lumens. The finding that imported polypeptides bind to a specific region of the VDAC protein implicates this channel in the process by which precursor proteins are recognized at and translocated across the mitochondrial outer membrane.
 ...
PMID:Binding of a synthetic targeting peptide to a mitochondrial channel protein. 138 May 5

Beta-amyloid (Abeta) deposition, in the form of plaques and amyloid angiopathy, and hyper-phosphorylated tau deposition forming neurofibrillary tangles, dystrophic neurites around beta-amyloid plaques and neuropil threads, are neuropathological hallmarks of Alzheimer's disease (AD) that accumulate in the brain with disease progression. These changes are accompanied by progressive loss of synapses and nerve cell death. Progressive cognitive impairment and dementia are the main neurological deficits. In addition, there is cumulative evidence demonstrating other metabolic disturbances that impair cell function and hamper neuron viability. The main components of the mitochondria are altered: complex IV of the respiratory chain is reduced; complex V which metabolizes ADP to form ATP is oxidatively damaged and functionally altered; and voltage-dependent anion channel VDAC, a major component of the outer mitochondrial membrane that regulates ion fluxes, is damaged as a result of oxidative stress. Mitochondria are a major source of reactive oxygen species that promote oxidative damage to DNA, RNA, proteins and lipids. Protein targets of oxidative damage are, among others, several enzymatic components of the glycolysis, lipid metabolism and cycle of the citric acid that fuel oxidative phosphorylation, mitochondrial respiration and energy production. The lipid composition of lipid rafts, key membrane specializations that facilitate the transfer of substrates, and protein-protein and lipid-protein interactions, is altered as a result of the abnormally low levels of n-3 long chain polyunsaturated fatty acids (mainly docosahexaenoic acid) that increase viscosity and augment energy consumption. Abnormal lipid raft composition may also modify the activity of key enzymes that modulate the cleavage of the amyloid precursor protein to form toxic Abeta. This is further complicated by the disruption of the complex VDAC with estrogen receptor alpha at the caveolae which participates, under physiological conditions, in the protection against beta-amyloid. Together, all these alterations converge in reduced energy production and increased energy demands in altered cells. Cell exhaustion is suggested as being a determining element to interpret impaired neuron function, reduced molecular turnover, and enhanced cell death.
 ...
PMID:Altered mitochondria, energy metabolism, voltage-dependent anion channel, and lipid rafts converge to exhaust neurons in Alzheimer's disease. 1979 58