Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP
Abstract
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 ≈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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- September 2005
- DOI:
- 10.1073/pnas.0506289102
- Bibcode:
- 2005PNAS..10213064C
- Keywords:
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- heme;
- nucleotide regulation;
- BIOCHEMISTRY, BIOLOGICAL SCIENCES