Abstract
Pulvomycin and the synonymous antibiotics labilomycin and 1063-Z are shown to inhibit prokaryotic protein synthesis by acting on elongation factor Tu (EF-Tu): in the presence of the antibiotic, the affinity of EF-Tu for guanine nucleotides is altered, the EF-Tu.GDP/GTP exchange is catalyzed, and the formation of the EF-Tu.GTP complex is stimulated. Hydrolysis of GTP by EF-Tu, induced by aminoacyl-tRNA, ribosomes, and mRNA or by kirromycin, is inhibited by pulvomycin. As shown by Millipore filtration, chromatographic analysis, and hydrolysis protection experiments, pulvomycin prevents interaction between aminoacyl-tRNA and EF-Tu.GTP to yield the ternary complex aminoacyl-tRNA.EF-Tu.GTP. Thus, enzymatic binding of aminoacyl-tRNA to ribosomes is blocked.
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- AKITA E., MAEDA K., UMEZAWA H. CHEMISTRY OF LABILOMYCIN. J Antibiot (Tokyo) 1964 Sep;17:200–215. [PubMed] [Google Scholar]
- AKITA E., MAEDA K., UMEZAWA H. ILOLATION AND CHARACTERIZATION OF LABILOMYCIN, A NEW ANTIBIOTIC. J Antibiot (Tokyo) 1963 Jul;16:147–151. [PubMed] [Google Scholar]
- Beres L., Lucas-Lenard J. Studies on the fluorescence of the Y base of yeast phenylalanine transfer ribonucleic acid. Effect of pH, aminoacylation, and interaction with elongation factor Tu. Biochemistry. 1973 Sep 25;12(20):3998–4002. doi: 10.1021/bi00744a033. [DOI] [PubMed] [Google Scholar]
- Blumenthal T., Douglass J., Smith D. Conformational alteration of protein synthesis elongation factor EF-Tu by EF-Ts and by kirromycin. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3264–3267. doi: 10.1073/pnas.74.8.3264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown S., Blumenthal T. Function and structure in ribonucleic acid phage Qbeta ribonucleic acid replicase. Effect of inhibitors of EF-Tu on ribonucleic acid synthesis and renaturation of active enzyme. J Biol Chem. 1976 May 10;251(9):2749–2753. [PubMed] [Google Scholar]
- Chinali G., Wolf H., Parmeggiani A. Effect of kirromycin on elongation factor Tu. Location of the catalytic center for ribosome-elongation-factor-Tu GTPase activity on the elongation factor. Eur J Biochem. 1977 May 2;75(1):55–65. doi: 10.1111/j.1432-1033.1977.tb11503.x. [DOI] [PubMed] [Google Scholar]
- Fischer E., Wolf H., Hantke K., Parmeggiani A. Elongation factor Tu resistant to kirromycin in an Escherichia coli mutant altered in both tuf genes. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4341–4345. doi: 10.1073/pnas.74.10.4341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gordon J. A stepwise reaction yielding a complex between a supernatant fraction from E. coli, guanosine 5'-triphosphate, and aminoacyl-sRNA. Proc Natl Acad Sci U S A. 1968 Jan;59(1):179–183. doi: 10.1073/pnas.59.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gordon J. Interaction of guanosine 5'-triphosphate with a supernatant fraction from E. coli and aminoacyl-sRNA. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1574–1578. doi: 10.1073/pnas.58.4.1574. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haenni A. L., Chapeville F. The behaviour of acetylphenylalanyl soluble ribonucleic acid in polyphenylalanine synthesis. Biochim Biophys Acta. 1966 Jan 18;114(1):135–148. doi: 10.1016/0005-2787(66)90261-9. [DOI] [PubMed] [Google Scholar]
- Hamel E., Koka M., Nakamoto T. Requirement of an Escherichia coli 50 S ribosomal protein component for effective interaction of the ribosome with T and G factors and with guanosine triphosphate. J Biol Chem. 1972 Feb 10;247(3):805–814. [PubMed] [Google Scholar]
- Kelmers A. D. Preparation of a highly purified phenylalanine transfer ribonucleic acid. J Biol Chem. 1966 Aug 10;241(15):3540–3545. [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Maehr H., Leach M., Yarmchuk L., Stempel A. Antibiotic X-5108. V. Structures of antibiotic X-5108 and mocimycin. J Am Chem Soc. 1973 Dec 12;95(25):8449–8450. doi: 10.1021/ja00806a043. [DOI] [PubMed] [Google Scholar]
- Maehr H., Williams T. H., Leach M., Stempel A. Antibiotic X-5108. VI. Relative configuration of the tetrahydrofuran moiety of goldinamine. Helv Chim Acta. 1974;57(1):212–213. doi: 10.1002/hlca.19740570127. [DOI] [PubMed] [Google Scholar]
- Pingoud A., Urbanke C., Krauss G., Peters F., Maass G. Ternary complex formation between elongation factor Tu, GTP and aminoacyl-tRNA: an equilibrium study. Eur J Biochem. 1977 Sep;78(2):403–409. doi: 10.1111/j.1432-1033.1977.tb11752.x. [DOI] [PubMed] [Google Scholar]
- Pingoud A., Urbanke C., Wolf H., Maass G. The binding of kirromycin to elongation factor Tu. Structural alterations are responsible for the inhibitory action. Eur J Biochem. 1978 May;86(1):153–157. doi: 10.1111/j.1432-1033.1978.tb12294.x. [DOI] [PubMed] [Google Scholar]
- Schwartz J. L., Tishler M., Arison B. H., Shafer H. M., Omura S. Identification of mycolutein and pulvomycin as aureothin and labilomycin respectively. J Antibiot (Tokyo) 1976 Mar;29(3):236–241. doi: 10.7164/antibiotics.29.236. [DOI] [PubMed] [Google Scholar]
- Tanaka N., Kinoshita T., Masukawa H. Mechanism of protein synthesis inhibition by fusidic acid and related antibiotics. Biochem Biophys Res Commun. 1968 Feb 15;30(3):278–283. doi: 10.1016/0006-291x(68)90447-6. [DOI] [PubMed] [Google Scholar]
- Wax R., Maises W., Weston R., Birnbaum J. Efrotomycin, a new antibiotic from Streptomyces lactamdurans. J Antibiot (Tokyo) 1976 Jun;29(6):670–673. doi: 10.7164/antibiotics.29.670. [DOI] [PubMed] [Google Scholar]
- Wolf H., Chinali G., Parmeggiani A. Kirromycin, an inhibitor of protein biosynthesis that acts on elongation factor Tu. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4910–4914. doi: 10.1073/pnas.71.12.4910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolf H., Chinali G., Parmeggiani A. Mechanism of the inhibition of protein synthesis by kirromycin. Role of elongation factor Tu and ribosomes. Eur J Biochem. 1977 May 2;75(1):67–75. doi: 10.1111/j.1432-1033.1977.tb11504.x. [DOI] [PubMed] [Google Scholar]
- Wolf H., Zähner H. Stoffwechselprodukte von Mikroorganismen. 99. Kirromycin. Arch Mikrobiol. 1972;83(2):147–154. [PubMed] [Google Scholar]