Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.5 (RNase P)
 1,348 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Inhibitory effects of arotinoids on tRNA biogenesis. 1109 76

Ribonuclease P (RNase P) is a ubiquitous and essential enzyme that endonucleolytically cleaves all tRNA precursors to produce the mature 5'-end. We have investigated the effect of synthetic rertinoids (all-trans retinoic acid, acitretin) and arotinoids (Ro 13-7410, Ro 15-0778, Ro, 13-6298 and Ro 15-1570) on RNase P activity isolated for the first time from normal human epidermal keratinocytes (NHEK). All tested compounds but one (Ro 15-1570) revealed a dose-dependent inhibition of RNase P activity, indicating that they may have a direct effect on tRNA biogenesis. Detailed kinetic analysis showed that all retinoids behave as classic competitive inhibitors. On the basis of the Ki values Ro 13-7410 was found to be the strongest inhibitor among all compounds tested.
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PMID:Retinoids inhibit human epidermal keratinocyte RNase P activity. 1271 96