Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitochondrial Mg2+-activated adenosine triphosphatase (ATPase; EC 3.6.1.4) from the insect flagellate Crithidia fasciculata ATCC 11745 has been extracted from the membrane by chloroform treatment and purified to electrophoretic homogeneity by a method involving ammonium sulphate fractionation, gel filtration on Sephadex G-200 and DEAE-cellulose chromatography. The molecular weight of the native enzyme, determined by gel filtration, was about 350 000. Five subunits were detected by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate, with molecular weights of 54 000, 45 000, 35 000, 20 000 and 10 000. The membrane-bound, but not the soluble (F1) ATPase was inhibited by oligomycin and leucinostatin. Both forms of the enzyme were strongly inhibited by the antibiotic efrapeptin and the trypanocidal drug suramin. The inhibition by efrapeptin was of the mixed type, with double-reciprocal plots intersecting below the abscissa, as in the case of the enzyme present in beef heart submitochondrial particles. Suramin, on the other hand, acted as a non-competitive inhibitor of the membrane-bound ATPase and as a strictly competitive inhibitor of the purified F1 ATPase.
 ...
PMID:Mg2+-activated adenosine triphosphatase from Crithidia fasciculata: purification and inhibition by suramin and efrapeptin. 611 95

Suramin is a polysulfonated naphthylurea developed originally to treat trypanosomiasis. This drug has gained considerable attention recently as an effective anticancer agent. Previous studies have demonstrated that suramin also is an antagonist of ATP at P2x purinergic receptors. In the present study suramin was shown to evoke Ca++ release from skeletal muscle sarcoplasmic reticulum (SR) vesicles in a concentration-dependent manner. Ca++ release was inducable from vesicles derived from junctional SR but not from those derived from longitudinal SR. This subcellular site-dependent specificity suggests that suramin's actions on muscle involve the Ca++ release channel (CRC), a protein unique to terminal cisternae. This channel has been established as the site of action of ryanoid alkaloids such as ryanodine and dehydroryanodine. Suramin did not mimic ryanoid actions on the SR CRC, nor did it competitively diminish ryanodine binding. Instead, suramin actually increased [3H]ryanodine binding to junctional SR membranes. In this respect, suramin exhibited agonist effects like those of the adenine nucleotide, beta,gamma-methyleneadenosine 5'-triphosphate. Suramin's mechanism of action did not involve oxidation of sulfhydryl groups on the SR CRC, because dithiothreitol (1 mM) had no effect on suramin-induced Ca++ release. Independently of its effects on the CRC, suramin inhibited the Ca(++)-adenosine triphosphatase (EC 3.6.1.38, SERCA1) of SR membrane vesicles. The ability of suramin to diminish ATP-dependent Ca++ accumulation by SR vesicles therefore reflects two distinct actions: 1) activation (opening) of the SR Ca++ release channel and 2) inhibition of the Ca++ pump.
 ...
PMID:Dual effect of suramin on calcium fluxes across sarcoplasmic reticulum vesicle membranes. 818 38