Search results for "adenosine triphosphate"
showing 10 items of 232 documents
Effect of ATP Binding and Hydrolysis on Dynamics of Canine Parvovirus NS1▿ †
2010
ABSTRACT The replication protein NS1 is essential for genome replication and protein production in parvoviral infection. Many of its functions, including recognition and site-specific nicking of the viral genome, helicase activity, and transactivation of the viral capsid promoter, are dependent on ATP. An ATP-binding pocket resides in the middle of the modular NS1 protein in a superfamily 3 helicase domain. Here we have identified key ATP-binding amino acid residues in canine parvovirus (CPV) NS1 protein and mutated amino acids from the conserved A motif (K406), B motif (E444 and E445), and positively charged region (R508 and R510). All mutations prevented the formation of infectious viruse…
Inside the Hsp90 inhibitors binding mode through induced fit docking
2009
Abstract During the last few decades, the development of new anticancer strategies had to face the instability of many tumors, occurring when the genetic plasticity of cells produces new drug-resistant cancers. It has been shown that a chaperone protein, heat shock protein 90 (Hsp90), is one of the fundamental factors involved in the cell response to stresses, and its role in many biochemical pathways has been demonstrated. Thus, the inhibition of Hsp90 represents a new target of antitumor therapy, since it may influence many specific signaling pathways. The natural antibiotic Geldanamycin is the first Hsp90 inhibitor that has been identified. Nevertheless, more potent and water-soluble sma…
Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor
2020
The P2X7 receptor (P2X7R) possesses a unique structure associated to an as yet not fully understood mechanism of action that facilitates cell permeability to large ionic molecules through the receptor itself and/or nearby membrane proteins. High extracellular adenosine triphosphate (ATP) levels—inexistent in physiological conditions—are required for the receptor to be triggered and contribute to its role in cell damage signaling. The inconsistent data on its activation pathways and the few studies performed in natively expressed human P2X7R have led us to review the structure, activation pathways, and specific cellular location of P2X7R in order to analyze its biological relevance. The ATP-…
8-N(3)-3'-biotinyl-ATP, a novel monofunctional reagent: differences in the F(1)- and V(1)-ATPases by means of the ATP analogue.
2001
A novel photoaffinity label, 8-N(3)-3'-biotinyl-ATP, has been synthesized. The introduction of an additional biotin residue is advantageous for easy detection of labeled proteins. This could be first tested by reaction with the F(1)-ATPase from the thermophilic bacterium PS3 (TF(1)). UV irradiation of TF(1) in the presence of 8-N(3)-3'-biotinyl-ATP results in a nucleotide-dependent binding of the analogue in the noncatalytic alpha and the catalytic beta subunits of TF(1), demonstrating the suitability of this analogue as a potential photoaffinity label. Reaction with the V(1)-ATPase, however, led to labeling of subunit E, which has been suggested as a structural and functional homologue of …
Mapping of a binding site for ATP within the extracellular region of the Torpedo nicotinic acetylcholine receptor beta-subunit.
1997
Using 2,8,5'-[H-3]ATP as a direct photoaffinity label for membrane-bound nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata, we have identified a binding site for ATP in the extracellular region of the beta-subunit of the receptor. Photolabeling was completely inhibited in the presence of saturating concentrations of nonradioactive ATP, whereas neither the purinoreceptor antagonists suramin, theophyllin, and caffeine nor the nAChR antagonists alpha-bungarotoxin and d-tubocurarine affected the labeling reaction. Competitive and noncompetitive nicotinic agonists and Ca2+ increased the yield of the photoreaction by up to 50%, suggesting that the respective binding sites are allost…
Inhibition of Eimeria tenella CDK-related kinase 2: From target identification to lead compounds.
2010
Apicomplexan parasites encompass several human- and animal-pathogenic protozoans such as Plasmodium falciparum, Toxoplasma gondii, and Eimeria tenella. E. tenella causes coccidiosis, a disease that afflicts chickens, leading to tremendous economic losses to the global poultry industry. The considerable increase in drug resistance makes it necessary to develop new therapeutic strategies against this parasite. Cyclin-dependent kinases (CDKs) are key molecules in cell-cycle regulation and are therefore prominent target proteins in parasitic diseases. Bioinformatics analysis revealed four potential CDK-like proteins, of which one—E. tenella CDK-related kinase 2 (EtCRK2)—has already been charact…
NANC inhibitory neurotransmission in mouse isolated stomach: Involvement of nitric oxide, ATP and vasoactive intestinal polypeptide
2003
1. The neurotransmitters involved in NANC relaxation and their possible interactions were investigated in mouse isolated stomach, recording the motor responses as changes of endoluminal pressure from whole organ. 2. Field stimulation produced tetrodotoxin-sensitive, frequency-dependent, biphasic responses: rapid transient relaxation followed by a delayed inhibitory component. 3. The inhibitor of the synthesis of nitric oxide (NO), L-NAME, abolished the rapid relaxation and significantly reduced the slow relaxation. Apamin, blocker of Ca 2+-dependent K + channels, or ADPβS, which desensitises P 2y purinoceptors, reduced the slow relaxation to 2-8 Hz, without affecting that to 16-32 Hz or the…
Photoaffinity cross-linking of F1ATPase from spinach chloroplasts by 3'-arylazido-beta-alanyl-8-azido ATP.
1994
UV irradiation of the ATPase (CF1) from spinach chloroplasts in the presence of 3'-arylazido-beta-alanyl-8-azido ATP (8,3'-DiN3ATP) results in a nucleotide-dependent inactivation of the enzyme and in a nucleotide-dependent formation of alpha-beta cross-links. The results demonstrate an interfacial localization of the nucleotide binding sites on CF1.
Energy-Linked Reactions Catalyzed by the Purified ATPase Complex (F0F1) from Rhodospirillum rubrum Chromatophores
1980
1. The isolation of the F0F1-ATPase complex from Rhodospirillum rubrum chromatophores by the use of taurodeoxycholate is described. 2. The enzyme preparation contains about 12 polypeptides; five are subunits of the F1 moiety. 3. The ATPase activity of the purified enzyme is dependent on the addition of phospholipids. 4. Km-vales for Mg2+-ATP and Ca2+-ATP are similar to the values obtained for the membrane-bound enzyme. 5. The F0F1-ATPase complex is more than 70% inhibited by oligomycin and N,N′-dicyclohexyl-carbodiimide. 6. The F0F1-ATPase complex was integrated into liposomes. The reconstituted proteoliposomes catalyzed energy transduction as shown by ATP-dependent quenching of acridine dy…
Metabolic classification of human rectal adenocarcinomas: a novel guideline for clinical oncologists?
2003
Based on previous findings in SCC of the human uterine cervix and of the head and neck, metastasis- and survival-related metabolic classification was performed in human rectal adenocarcinomas. Such a characterization is suggested as basis of a novel clinical guideline for an appropriate therapy of epithelium-derived malignancies.Tissue concentrations of ATP, glucose, and lactate in viable tumor regions of 33 pretherapeutically taken cryobiopsies from 24 patients were measured at a microscopic level using the technique of imaging bioluminescence.In metastatic carcinomas, lactate levels were significantly higher (mean+/-SD: 13.4+/-3.8 vs 6.9+/-2.5 micro mol/g, P = 0.0046) and glucose levels s…