Interaction of diphtheria toxin with phosphorylated molecules.
The binding of diphtheria toxin to 125I-labeled cell surface glycoproteins from hamster thymocytes was shown to be inhibited by nucleotides. The relative effectiveness of the nucleotides (at 5 mM) was found to be thymidine triphosphate greater than adenosine triphosphate greater than guanosine triphosphate greater than uridine triphosphate greater than cytidine triphosphate. When adenine-containing compounds were used, the relative effectiveness was determined to be adenosine tetraphosphate greater than adenosine triphosphate greater than adenosine diphosphate greater than adenosine monophosphate. In addition, tetrapolyphosphate, tripolyphosphate, inositol hexaphosphate (phytic acid), and the highly phosphorylated proteins casein and phosvitin were also shown to be potent inhibitors of the binding of diphtheria toxin to 125I-labeled cell surface glycoproteins. Diphtheria toxin was shown to bind directly to 125I-casein; this binding was also inhibited by the highly phosphorylated compounds and was decreased by pretreatment of the 125I-casein with alkaline phosphatase. These results suggest that diphtheria toxin binds to regions of high phosphate density and raise the possibility that the site on the cell surface glycoproteins to which diphtheria toxin binds might be polyanionic in nature.
D000227:Adenine Nucleotides / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002241:Carbohydrates / Q000494:pharmacology; D002364:Caseins / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D006224:Cricetinae; D004167:Diphtheria Toxin / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009711:Nucleotides / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology*; D010750:Phosphoproteins / Q000494:pharmacology; D010766:Phosphorylation; D011122:Polyphosphates / Q000494:pharmacology; D011485:Protein Binding
D000227:Adenine Nucleotides; D000596:Amino Acids; D002241:Carbohydrates; D002364:Caseins; D002614:Chelating Agents; D004167:Diphtheria Toxin; D006023:Glycoproteins; D008565:Membrane Proteins; D009711:Nucleotides; D010710:Phosphates; D010750:Phosphoproteins; D011122:Polyphosphates