Jonathan Winger - Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP

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      PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED   STATES OF AMERICA Volume: 102 Issue: 37 Pages: 13064-13069   Published:SEP 13 2005


      Nitric oxide (NO) affects many physiological systems by   activating cGMP signaling cascades through soluble guanylate   cyclase (sGC). In the accepted model, NO binds to the sGC heme,   activating the enzyme. Here, we report that in the presence of   physiological concentrations of ATP and GTP, NO dissociation from   the sGC heme is approximate to 160 times slower than the rate of   enzyme deactivation in vitro. Deactivated sGC still has NO bound   to the heme, and full activation requires additional NO. We   propose an activation model where, in the presence of both ATP   and GTP, tonic NO forms a stable heme complex with low sGC   activity; acute production of NO transiently and fully activates   this NO-bound sGC.

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