Formycin triphosphate as a probe for the ATP binding site involved in the activation of guanylate cyclase

Abstract

Formycin A triphosphate (FTP), a fluorescent analog of ATP, slightly increased basal guanylate cyclase activity, but significantly potentiated guanylate cyclase activity stimulated by atrial natriuretic factor (ANF) in rat lung membranes. FTP potentiated ANF-stimulated guanylate cyclase activity with an EC 50 at about 90 μM and inhibited ATP-stimulated guanylate cyclase activity with an IC 50 at about 100 μM. These results indicate that FTP binds more tightly than ATP for the same binding site. Therefore, FTP would be an excellent tool for studying the ATP binding site.