Biomaterial Database

Inhibition of HeLa cell DNA topoisomerase I by ATP and phosphate. 1985

R L Low, and J A Holden

The relaxation activity of DNA topoisomerase I from HeLa cell nuclei is strongly inhibited by a variety of purine nucleotides in the presence but not absence of 1 mM potassium phosphate. For ATP, 3-4 mM causes nearly complete inhibition. The 2'-and 3'-AMP isomer are active as well in the presence of 1 mM phosphate, but the 5'-AMP isomer and adenosine are inert. At 3 mM ATP, the titration curve for phosphate is sigmoidal with inhibition beginning abruptly at about 0.5 mM. The negatively-supercoiled DNA isolated from an "inhibited" reaction is relaxed as well as the standard DNA template in the absence of ATP and phosphate suggesting that inhibition does not result from an alteration of the template which protects against its relaxation. Relaxation of positively-supercoiled DNA is also inhibited. Catalysis by E. coli DNA topoisomerase I and HeLa DNA topoisomerase II is not inhibited at concentrations of ATP and phosphate sufficient to cause 80-90% inhibition of HeLa type 1 enzyme.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010710	Phosphates	Inorganic salts of phosphoric acid.	Inorganic Phosphate,Phosphates, Inorganic,Inorganic Phosphates,Orthophosphate,Phosphate,Phosphate, Inorganic
D011685	Purine Nucleotides	Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA.	Nucleotides, Purine
D004278	DNA, Superhelical	Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.	DNA, Supercoiled,DNA, Supertwisted,Supercoiled DNA,Superhelical DNA,Supertwisted DNA
D004926	Escherichia coli	A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.	Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D006367	HeLa Cells	The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays.	Cell, HeLa,Cells, HeLa,HeLa Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000255	Adenosine Triphosphate	An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.	ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D059004	Topoisomerase I Inhibitors	Compounds that inhibit the activity of DNA TOPOISOMERASE I.	DNA Topoisomerase I Inhibitor,DNA Topoisomerase III Inhibitor,DNA Topoisomerase III Inhibitors,DNA Type 1 Topoisomerase Inhibitor,DNA Type III Topoisomerase Inhibitor,DNA Type III Topoisomerase Inhibitors,Topoisomerase 1 Inhibitor,Topoisomerase 1 Inhibitors,Topoisomerase 3 Inhibitor,Topoisomerase 3 Inhibitors,Topoisomerase I Inhibitor,Topoisomerase III Inhibitor,Topoisomerase III Inhibitors,DNA Topoisomerase I Inhibitors,DNA Type 1 Topoisomerase Inhibitors,1 Inhibitor, Topoisomerase,3 Inhibitor, Topoisomerase,3 Inhibitors, Topoisomerase,I Inhibitor, Topoisomerase,III Inhibitor, Topoisomerase,III Inhibitors, Topoisomerase,Inhibitor, Topoisomerase 1,Inhibitor, Topoisomerase 3,Inhibitor, Topoisomerase I,Inhibitor, Topoisomerase III,Inhibitors, Topoisomerase 1,Inhibitors, Topoisomerase 3,Inhibitors, Topoisomerase I,Inhibitors, Topoisomerase III