The hepatic adenylate cyclase system. I. Evidence for transition states and structural requirements for guanine nucleotide activation

Y. Salomon, M. C. Lin, C. Londos, M. Rendell, M. Rodbell

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Abstract

Previous studies showed that guanine nucleotides, acting at a site termed the nucleotide regulatory site, are required for activation of hepatic adenylate cyclase, and that glucagon facilitates this process. This study shows that only guanine nucleotides containing triphosphate groups at the 5' position of ribose (or 3' deoxyribose) are capable of activating the enzyme. The terminal phosphate is not utilized in the activation process, since 5' guanylylimidodiphosphate [Gpp(NH)p] and 5' guanylyl methylenediphosphonate, analogues of guanosine triphosphate that are not utilized in transferase or hydrolase reactions, stimulate enzyme activity. The nucleotides bind in their free form at the regulatory site; chelation by magnesium ion shifts the apparent concentration dependence for activation by Gpp(NH)p. Guanosine diphosphate inhibits competitively Gpp(NH)p stimulated activity and inhibits basal activity and activities stimulated by glucagon.

Original languageEnglish (US)
Pages (from-to)4239-4245
Number of pages7
JournalJournal of Biological Chemistry
Volume250
Issue number11
StatePublished - Dec 1 1975

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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