Inhibition of bacterial RNA polymerase by the cyanobacterial metabolites 12-epi-hapalindole E isonitrile and calothrixin A.
The alkaloid 12-epi-hapalindole E isonitrile, from a cyanobacterial Fischerella species, and the indolophenanthridine calothrixin A, from Calothrix, inhibited Escherichia coli RNA polymerase competitively with respect to ATP, and non-competitively with respect to UTP. The inhibition was dependent on the order of addition of the inhibitors. The K(I) values, with ATP as the variable substrate, were 1.3+/-0.2 mM and 0.23+/-0.11 mM, respectively. Based on comparisons with the sensitivity of whole cells to these inhibitors, it is concluded that other targets in addition to RNA polymerase may also be implicated in their action.
Division of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Science, The Australian National University, Canberra, A.C.T. 2000, Australia.
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Doan
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Stewart
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Smith
D000458:Cyanobacteria / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D026121:Indole Alkaloids; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D012329:RNA, Bacterial; D014158:Transcription, Genetic
C433882:12-epi-hapalindole E isonitrile; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007211:Indoles; D012329:RNA, Bacterial; C418328:calothrixin A; D012321:DNA-Directed RNA Polymerases