Biomaterial Database

Interaction of substrate analogues with Escherichia coli DNA-dependent RNA polymerase. 1976

V W Armstrong, and F Eckstein

The inhibition of RNA polymerase with ATP and UTP analogues modified in the phosphate and ribose moieties has been investigated. 1. Modification of the terminal phosphate with a loss of the negative charge [adenosine 5'-(3-O-methyl)triphosphate, Ki = 1.75 mM] substantially weakens the binding ability of these analogues to the enzyme whereas modification with retention of the charge is not so detrimental [adenosine tetraphosphate, Ki = 0.17 mM]. 2. 2'-Modified analogues are only weak competitive inhibitors [2'-amino-2'-deoxyadenosine 5'-triphosphate, Ki = 2.3 mM] of their corresponding substrates [ATP, Km = 0.07 mM] whereas 3'-modified analogues are extremely potent in their inhibition [3'-amino-3'-deoxyadenosine 5'-triphosphate, Ki = 2.3 muM]. 3. A difference was observed in the inhibition of the elongation step of RNA polymerase by ATP and UTP analogues. Thus ATP analogues showed a strong binding to the CT form of the poly[d(A-T)] ternary complex and only a weak binding to the CA form. UTP analogues, on the other hand, showed a similar binding to both forms of the complex.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds 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
D012265	Ribonucleotides	Nucleotides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)	Ribonucleoside Phosphates,Ribonucleotide,Phosphates, Ribonucleoside
D012321	DNA-Directed RNA Polymerases	Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).	DNA-Dependent RNA Polymerases,RNA Polymerases,Transcriptases,DNA-Directed RNA Polymerase,RNA Polymerase,Transcriptase,DNA Dependent RNA Polymerases,DNA Directed RNA Polymerase,DNA Directed RNA Polymerases,Polymerase, DNA-Directed RNA,Polymerase, RNA,Polymerases, DNA-Dependent RNA,Polymerases, DNA-Directed RNA,Polymerases, RNA,RNA Polymerase, DNA-Directed,RNA Polymerases, DNA-Dependent,RNA Polymerases, DNA-Directed
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships