Diphtheria Toxin-dependent Adenosine Diphosphate Ribosylation of Aminoacyl Transferase II and Inhibition of Protein Synthesis

T Honjo,Y Nishizuka,O Hayaishi,I Kato

doi:10.1016/s0021-9258(18)93347-8

T Honjo, Y Nishizuka + Show 2 more

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https://doi.org/10.1016/s0021-9258(18)93347-8

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Abstract

In the presence of diphtheria toxin, the adenosine diphosphate ribose portion of nicotinamide adenine dinucleotide was transferred to aminoacyl transferase II obtained from rat liver. The reaction resulted in a concurrent inactivation of this particular enzyme, one of the supernatant factors which assemble amino acids into polypeptide chain. The linkage of ADP-ribose to aminoacyl transferase II appeared to be of covalent nature. The reaction was reversible. Diptheria toxin may act as an enzyme or a catalytic cofactor in this reaction.

Highlights

In the presence of diphtheria toxin, the adenosine diphosphate ribose portion of nicotinamide adenise dinucleotide was transferred to aminoacyl transferase II obtained from rat liver
The activity of polypeptide synthesis was assayed by measuring the poly U-dependent incorporation of radioactivity from rGphenylalanyl-tRNA
Rat liver ribosomes were prepared according to the method of Skogerson and Moldave [6], and further washed by sucrose density gradient centrifugation

Summary

From the Department

In the presence of diphtheria toxin, the adenosine diphosphate ribose portion of nicotinamide adenise dinucleotide was transferred to aminoacyl transferase II obtained from rat liver. The reaction resulted in a concurrent inactivation of this particular enzyme, one of the supernatant factors which assemble amino acids into polypeptide chain. Diphtheria toxin inhibits mammalian protein synthesis in cell-free systems as well as in cultured cells (l-3). Has shown that diphtheria toxin inactivates aminoacyl transferase II obtained from rabbit reticulocytes. Experiments to be reported here indicate that in the presence of diphtheria toxin the ADP-ribose portion of NAD is transferred to transferase II,’ resulting in a concurrent inactivation of this particular enzyme. I and II, two complementary supernatant factors, were purified from rat liver by a modification of the method of Skogerson and Moldave [6]. $ Recipient of Postgraduate Fellowship of Sigma Chemical Company. 1 The abbreviations used are: transferases I and II, aminoacyl transferases I and II; poly U, polyuridylic acid; tRNA, transfer ribonucleic acid; TCA, trichloracetic acid

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