Inhibition by Siomycin and Thiostrepton of Both Aminoacyl-tRNA and Factor G Binding to Ribosomes

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1971 Aug 1

PMID 4331558

Citations 34

Authors

J Modolell

B Cabrer

A Parmeggiani

D Vazquez

Affiliations

Soon will be listed here.

Abstract

Siomycin, a peptide antibiotic that interacts with the 50S ribosomal subunit and inhibits binding of factor G, is shown also to inhibit binding of aminoacyl-tRNA; however, it does not impair binding of fMet-tRNA and completion of the initiation complex. Moreover, unlike other inhibitors of aminoacyl-tRNA binding (tetracycline, sparsomycin, and streptogramin A), siomycin completely abolishes the GTPase activity associated with the binding of aminoacyl-tRNA catalyzed by factor T(u). A single-site interaction of siomycin appears to be responsible for its effect on both the binding of the aminoacyl-tRNA-T(u)-GTP complex and that of factor G.

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References

Modolell J, Davis B . Rapid inhibition of polypeptide chain extension by streptomycin. Proc Natl Acad Sci U S A. 1968; 61(4):1279-86. PMC: 225252. DOI: 10.1073/pnas.61.4.1279. View

Weisblum B, Davies J . Antibiotic inhibitors of the bacterial ribosome. Bacteriol Rev. 1968; 32(4 Pt 2):493-528. PMC: 413162. View

NISHIZUKA Y, LIPMANN F . The interrelationship between guanosine triphosphatase and amino acid polymerization. Arch Biochem Biophys. 1966; 116(1):344-51. DOI: 10.1016/0003-9861(66)90040-3. View

Modolell J, Davis B . Breakdown by streptomycin of initiation complexes formed on ribosomes of Escherichia coli. Proc Natl Acad Sci U S A. 1970; 67(3):1148-55. PMC: 283330. DOI: 10.1073/pnas.67.3.1148. View

BODLEY J, Lin L . Interaction of E. coli G factor with the 50S ribosomal subunit. Nature. 1970; 227(5253):60-1. DOI: 10.1038/227060a0. View

BRETSCHER M, Marcker K . Polypeptidyl-sigma-ribonucleic acid and amino-acyl-sigma-ribonucleic acid binding sites on ribosomes. Nature. 1966; 211(5047):380-4. DOI: 10.1038/211380a0. View

Ono Y, Skoultchi A, Waterson J, Lengyel P . Stoichiometry of aminoacyl-transfer RNA binding and GTP cleavage during chain elongation and translocation. Nature. 1969; 223(5207):697-701. DOI: 10.1038/223697a0. View

Weisblum B, Demohn V . Inhibition by thiostrepton of the formation of a ribosome-bound guanine nucleotide complex. FEBS Lett. 1970; 11(3):149-152. DOI: 10.1016/0014-5793(70)80515-4. View

Pestka S . Studies on the formation of transfer ribonucleic acid-ribosome complexes. XI. Antibiotic effects on phenylalanyl-oligonucleotide binding to ribosomes. Proc Natl Acad Sci U S A. 1969; 64(2):709-14. PMC: 223402. DOI: 10.1073/pnas.64.2.709. View

10.

Pestka S . Thiostrepton: a ribosomal inhibitor of translocation. Biochem Biophys Res Commun. 1970; 40(3):667-74. DOI: 10.1016/0006-291x(70)90956-3. View

11.

Tanaka N, Kinoshita T, Masukawa H . Mechanism of protein synthesis inhibition by fusidic acid and related antibiotics. Biochem Biophys Res Commun. 1968; 30(3):278-83. DOI: 10.1016/0006-291x(68)90447-6. View

12.

Kolakofsky D, Dewey K, Hershey J, Thach R . Guanosine 5'-triphosphatase activity of initiation factor f2. Proc Natl Acad Sci U S A. 1968; 61(3):1066-70. PMC: 305436. DOI: 10.1073/pnas.61.3.1066. View

13.

Shorey R, RAVEL J, Garner C, SHIVE W . Formation and properties of the aminoacyl transfer ribonucleic acid-guanosine triphosphate-protein complex. J Biol Chem. 1969; 244(17):4555-64. View

14.

MOLDAVE K, GALASINSKI W, Rao P, Siler J . Studies on the peptidyl tRNA translocase from rat liver. Cold Spring Harb Symp Quant Biol. 1969; 34:347-56. DOI: 10.1101/sqb.1969.034.01.041. View

15.

Weisblum B, Demohn V . Thiostrepton, an inhibitor of 5OS ribosome subunit function. J Bacteriol. 1970; 101(3):1073-5. PMC: 250429. DOI: 10.1128/jb.101.3.1073-1075.1970. View

16.

Ono Y, Skoultchi A, Waterson J, Lengyel P . Peptide chain elongation: GTP cleavage catalysed by factors binding aminoacyl-transfer RNA to the ribosome. Nature. 1969; 222(5194):645-8. DOI: 10.1038/222645a0. View

17.

Modolell J, Vazquez D, MONRO R . Ribosomes, G-factor and siomycin. Nat New Biol. 1971; 230(12):109-12. DOI: 10.1038/newbio230109a0. View

18.

Nirenberg M, Leder P . RNA CODEWORDS AND PROTEIN SYNTHESIS. THE EFFECT OF TRINUCLEOTIDES UPON THE BINDING OF SRNA TO RIBOSOMES. Science. 1964; 145(3639):1399-407. DOI: 10.1126/science.145.3639.1399. View

19.

Celma M, MONRO R, Vazquez D . Substrate and antibiotic binding sites at the peptidyl transferase centre of E. coli ribosomes: Binding of UACCA-Leu to 50 S subunits. FEBS Lett. 1971; 13(4):247-251. DOI: 10.1016/0014-5793(71)80546-x. View

20.

Steitz J . Polypeptide chain initiation: nucleotide sequences of the three ribosomal binding sites in bacteriophage R17 RNA. Nature. 1969; 224(5223):957-64. DOI: 10.1038/224957a0. View