Biomaterial Database

Inhibitory effects of arotinoids on tRNA biogenesis. 2000

E Papadimou, and A Monastirli, and D Tsambaos, and H F Merk, and D Drainas

Department of Biochemistry, School of Medicine, University of Patras, Greece.

The effects of five arotinoids (Ro 13-7410, Ro 15-0778, Ro 15-1570, Ro 13-6298, Ro 40-8757) on ribonuclease P (RNase P) activity were studied in a cell-free system derived from Dictyostelium discoideum. RNase P is a ribonucleoprotein that endonucleolytically cleaves all tRNA precursors to produce the mature 5' end. Kinetic analysis showed that these compounds behave as classical competitive inhibitors with Ki values 4.35, 3.6, 2.8 and 0.045 mM for Ro 13-6298, Ro 15-1570, Ro 15-0778 and Ro 13-7410, respectively. Ro 13-7410 was 62, 80 and 97 times more potent in inhibiting the enzyme activity as compared to Ro 15-0778, Ro 15-1570 and Ro 13-6298, respectively, whereas Ro 40-8757 showed no effect on RNase P activity. These results project the significance of the acidic polar terminus in the arotinoid molecule binding to the enzyme. The kinetics of inhibition reflects allosteric interactions of arotinoids with D. discoideum RNase P. Moreover, our findings indicate that the inhibitory effects of arotinoids on tRNA biogenesis can be mediated through mechanisms not involving the retinoid nuclear receptors.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D003864	Depression, Chemical	The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.	Chemical Depression,Chemical Depressions,Depressions, Chemical
D004023	Dictyostelium	A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.	Dictyostelium discoideum,Dictyostelium discoideums,Dictyosteliums,discoideum, Dictyostelium
D004722	Endoribonucleases	A family of enzymes that catalyze the endonucleolytic cleavage of RNA. It includes EC 3.1.26.-, EC 3.1.27.-, EC 3.1.30.-, and EC 3.1.31.-.	Endoribonuclease
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012176	Retinoids	A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization.	Retinoid
D012343	RNA, Transfer	The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains.	Suppressor Transfer RNA,Transfer RNA,tRNA,RNA, Transfer, Suppressor,Transfer RNA, Suppressor,RNA, Suppressor Transfer
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
D016337	RNA, Catalytic	RNA that has catalytic activity. The catalytic RNA sequence folds to form a complex surface that can function as an enzyme in reactions with itself and other molecules. It may function even in the absence of protein. There are numerous examples of RNA species that are acted upon by catalytic RNA, however the scope of this enzyme class is not limited to a particular type of substrate.	Catalytic RNA,Ribozyme,Ribozymes